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E Michels

Publications and source records attributed to E Michels.

At least 37 records · Page 2Linked to original sources
PubMed1987

Murine alpha-2-macroglobulin: localization on a subpopulation of macrophages.

We have previously shown that mouse peritoneal macrophages synthesize and secrete alpha-2-macroglobulin (alpha 2M) in culture. We have now examined whether alpha 2M delineates a subpopulation of murine macrophages. Mouse alpha 2M was purified from plasma by gel filtration and immunoabsorption to remove IgM. Purified alpha 2M was an active proteinase inhibitor, had a pI of 4.8, and a relative molecular mass (Mr) of 765 kD which dropped to 194 kD on reduction. Antisera raised against mouse alpha 2M were not cross-reactive with guinea pig or human alpha 2M, or with antigens in guinea pig, human, bovine or equine serum. One to 18 per cent of freshly isolated bone marrow, resident peritoneal or induced peritoneal macrophages displayed immunoreactive cytoplasmic and surface alpha 2M as detected by single cell immunoperoxidase assay or flow cytometry. alpha 2M was not detected in or on thymocytes or bone marrow lymphocytes. In culture, bone marrow-derived macrophages displayed peak levels of cytoplasmic alpha 2M on day 7 and two peaks of surface alpha 2M on days 2-3 and 5-7. The fact that alpha 2M can function as an anti-proteinase, can modulate lymphokine production and is present on inflammatory macrophages suggests a regulatory role for macrophages bearing and secreting this molecule at tissue sites of inflammation.

Animals↗
PubMed1986

A monoclonal antibody against an antigen present on mouse macrophages and absent from monocytes.

A monoclonal antibody (BM8) raised in the rat against cultured mouse bone marrow-derived macrophages reacted only with macrophages and not with granulocytes, mast cells, platelets, lymphocytes, fibroblasts, and endothelial cells. BM8 did not detect blood monocytes. In cultured bone-marrow cells, expression of BM8-antigen was found on a few macrophages after one day of culture and reached its maximum level with 80% positive macrophages after 7-10 days of culture. The antibody BM8 belonged to the IgG2a subclass, was non-cytotoxic and directed against a 125 kD membrane antigen. In cryostat sections of normal mouse tissues (spleen, lymph node, thymus, liver, skin) BM8 detected tissue-fixed macrophages and Langerhans cells in the skin. In spleen and lymph node, BM8 reacted with macrophages in the red pulp and in the medullary cords, respectively, but not with heavily phagocytosing marginal-zone macrophages, as revealed by in-vivo phagocytosis of colloidal carbon. In granulomata induced by complete Freund's adjuvant, BM8 detected inflammatory macrophages but not epithelioid cells. Thus, antibody BM8 detected a differentiation antigen expressed only on mature, tissue-fixed macrophages.

Animals↗
PubMed1984

Functional characteristics of murine macrophages responding to migration inhibitory factors.

Mouse bone marrow cells differentiate in culture in the presence of L cell-conditioned medium to macrophages (M phi). Proliferation, release of plasminogen activator, expression of transglutaminase, random motility and response to a standard preparation of purified M phi migration inhibitory factor (MIF) was recorded daily up to 14 days. After an initial phase of proliferation, precursor cells differentiated into M phi. In the course of maturation, plasminogen activator production was transiently expressed between day 4 and 12; beginning on day 5 the cells expressed intracellular transglutaminase. Random motility of cells was high at the beginning of culture but steadily declined thereafter. The response to MIF was only expressed between day 5 and 8. However, it was possible to induce MIF responsiveness in mature, unresponsive M phi by the addition of L cell-conditioned medium. To characterize the MIF-responsive M phi type further, bone marrow-derived M phi at day 6 of culture were separated on a hypotonic Percoll gradient into three distinct cell bands. While all densities of M phi displayed random migration, only cells with a density between 1.060 and 1.065 were responsive to MIF. We conclude that the response of M phi to MIF is a phenotypic trait transiently expressed in the course of maturation.

Acyltransferases↗
PubMed1984

Migration inhibitory factors and macrophage differentiation.

It has been described before that only certain types of macrophages are capable to respond to lymphokines and that only certain macrophage phenotypes were able to migrate and to respond to migration inhibitory factors (MIF). With respect to the dissociation of MIF activities from a series of other biological activities, and with regard to the phenotype-associated response of macrophages to MIF it was asked: What are the characteristics of the MIF-responsive macrophage phenotype and what are the functional changes induced by MIF on macrophages in addition to inhibition of random migration? Bone marrow-derived macrophages on day 6 of culture were separated by hypotonic Percoll density gradient centrifugation into three distinct bands and analyzed for a variety of functions. It was found that migrating and MIF-responsive macrophages accumulate at a certain density. These macrophages were further characterized by monoclonal antibodies generated against murine macrophage phenotypes. One marker was found to be preferentially expressed by MIF-responsive macrophages. In order to study the inducibility of MIF responsiveness, bone marrow-derived macrophages on day 16 of culture which were poorly migrating and did not respond to MIF were induced to proliferate by the addition of L cell-conditioned medium. After proliferation had subsided, MIF sensitivity was restored. The effects of MIFs other than migration inhibition, on a number of functions which had been mapped within the cell cycle, were investigated. It was found that MIF acts anti-proliferative on "young", cycling macrophages. Non-cycling, mature macrophages were shifted to a state characterized by a decreased expression of transglutaminase and plasminogen activator and an increase of certain phenotypic surface markers. It is concluded that MIFs are differentiation-inducing signals, acting on the generation of macrophages from precursors but also in the recruitment of terminally differentiated macrophages to "inflammatory" type of macrophages which are functional in the induction of immune responses.

Animals↗
PubMed1984

Selection of the delayed hypersensitivity T effector and T suppressor cell response by antigen-presenting macrophages.

The T effector lymphocytes of delayed type hypersensitivity reactions (TDH) are regulated by a complex T suppressor (Ts) cell circuit. Induction of TDH cells requires Ia+ adherent cells as antigen-presenting cells. Little is known about the antigen presentation of the induction of Ts cells. We describe an experimental model in which TDH and Ts cells are induced separately by different antigen-presenting macrophages grown from bone marrow stem cells. Bone marrow derived macrophages grown in L cell-conditioned medium for various periods and labeled with 2,4-dinitrobenzene sulfonic acid differ in their ability to induce TDH and Ts cells in vitro. The functional activity of the two T subpopulations was assessed in vivo by epicutaneous challenge or sensitization with 2,4-dinitrofluorobenzene of mice receiving the in vitro educated cells. Ear swelling or suppression of swelling was recorded. It could be shown that 5-7 day bone marrow-derived DNP-labeled macrophages preferentially induced Thy 1+ Lyt 1+ antigen-specific TDH cells; 7-10 day old antigen-presenting bone marrow-derived macrophages induced preferentially Thy 1+ Lyt 2+ antigen specific Ts cells. Characterization of various phenotypic markers revealed different surface antigen expression and functional differences such as MIF responsiveness or transglutaminase activity on the two macrophage populations. These data support the concept that activation of the Ts regulatory circuit may require antigen presentation by specialized antigen presenting cells, characterized by certain surface and functional markers and different from those inducing preferentially TDH cells.

Animals↗
PubMed1984

[Chemical and functional characterization of lymphokines].

Macrophages are heterogeneous with respect to a number of constitutive and inducible functions. In order to study the underlying biological principle, a bone marrow liquid culture system was adopted in which bone marrow cells proliferate and differentiate into macrophages. It was found that maturing macrophages express various constitutive or inducible functions in an ordered sequence. The kinetics of their appearance and disappearance are dependent on the proliferative activity of macrophages. Macrophages in "late" G-1 of the cell cycle express constitutive functions like plasminogen activator production and are inducible by bacterial lipopolysaccharides, Poly I:C and lymphokines to release interferons. The response to lymphokines like migration inhibitory factor (MIF) and chemotactic factors is also transiently expressed during maturation. Using purified MIF, its influence on proliferation, differentiation and activation of macrophages was investigated. The changes induced were monitored following the expression of marker enzymes and of phenotype associated cell surface antigens using monoclonal antibodies. The results showed that functional changes induced by MIF on macrophages are limited and are not related to certain macrophage activating activities (MAF). As determined by flow cytofluorometry, transglutaminase expression and proliferation is consistently down-regulated by MIFs. This together with the shift and the expression of surface antigens indicates that MIFs provide a differentiation signal for a "young" macrophage to become more mature.

Animals↗
PubMed1983

Measurement in physical therapy. On the rules for assigning numerals to observations.

This paper discusses certain issues of theory, concept, definition, and method in measurement that are of concern to physical therapy. The topics discussed include the place of measurement in science, definitions of measurement, direct and indirect measurement, the logical requirements of measurement, scales of measurement, precision and accuracy, and reliability and validity. Comments pertinent to physical therapy are included in the discussion, and the issues are summarized by a look at the complex problems of using EMG for measurement of muscle activity.

Electromyography↗
PubMed1982

Evaluation and research in physical therapy.

The profession of physical therapy has a obligation to evaluate its many treatment and testing methods to ascertain their value, importance, and usefulness. Our evaluation of what we do must be based on measurement and research in physical therapy. The principles of measurement and research are discussed in some detail. The four scales of measurement, and the data they produce, are described. Test reliability and validity are discussed. Research is defined and its two principal forms, experimental and correlational, are discussed. The use of these principles in evaluating physical therapy treatment and testing methods is described by using clinical examples.

Humans↗
PubMed1976

Research and human rights. Part 1.

The problem of biomedical research and human rights is reviewed from the perspectives of current issues, historical events, and other sciences. Government control of research, reactions to and possible consequences of that control, and the concern for consent from members of vulnerable populations are examined. The nature of research is discussed and the origins of opposing ethical views are described in an attempt to clarify the issues within the problem.

Animals↗
PubMed1976

Guidelines for meetings.

The major purpose of a meeting is to make decisions. The most basic and important elements of conducting a meeting, preparing motions for consideration, and recording the decisions are presented. The use of the guidelines for more or less formal meetings is discussed.

Congresses as Topic↗
PubMed1975

On becoming a confederation.

This paper was presented as the keynote speech at the Seventh International Congress of the World Confederation for Physical Therapy. The question of what it will take to strengthen physical therapy as a world force for the health of mankind is examined. The past and present status of physical therapy and the Confederation are assessed as background for looking at ways to help the Confederation become truly a World Confederation for Physical Therapy.

History, 20th Century↗