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Biomedical subjects

C G Cochrane

Publications and source records attributed to C G Cochrane.

At least 181 records · Page 10Linked to original sources
PubMed1971

Acute immune complex disease in rabbits. The role of complement and of a leukocyte-dependent release of vasoactive amines from platelets.

By depletion of C3 from rabbits undergoing acute experimental immune complex disease with an anticomplementary factor in cobra venom, it has been possible to demonstrate that deposition of the complexes in arteries and glomeruli does not require the complement components reacting after C2. Immunological reactions, in which platelets release their vasoactive amines, have been examined in rabbits undergoing immune complex disease. A correlation was obtained between the presence of a complement-independent reaction which required blood leukocytes, antigen and platelets, the deposition of immune complexes, and the induction of glomerulonephritis. C3 depletion did, however, have a marked alleviating effect on the severity of the arterial lesions. Neutrophil accumulation and the subsequent necrotizing arteritis were prevented. In contrast, the character and severity of the glomerulonephritis was not altered by depletion of later-acting complement components.

Animals↗
PubMed1969

Isolation of a fragment (C3a) of the third component of human complement containing anaphylatoxin and chemotactic activity and description of an anaphylatoxin inactivator of human serum.

A small fragment of C3, called C3a, which has smooth muscle contracting activity, was isolated by three different methods. At pH 8.6, C3a behaved as cation, and using the Archibald method, its mol wt was determined to be 7000. A specific antiserum to C3a showed the fragment to be antigenically distinct from the rest of the C3 molecule, i.e., the C3b portion. The same antiserum and an anti-whole C3 were able to inhibit the biologic activity of C3a. In addition to anaphylatoxin activity, leukocyte chemotactic activity was shown to reside in C3a. Treatment with trypsin caused the cationic fragment to become anionic and abolished the anaphylatoxin but not the chemotactic activity. C3a fragments with identical biologic activity and comparable cationic properties, as determined by acid disc electrophoresis, were obtained by treatment of C3 with C3 convertase, C3 inactivator complex, trypsin, and plasmin. Thrombin produced a similar C3 fragment which was inactive. It was concluded that C3a corresponds to an unusually basic portion of C3 which may be liberated by attack of a variety of enzymes on a highly susceptible region of the native C3 molecule. C3b was cleaved by trypsin and less efficiently by thrombin or plasmin into two antigenically distinct pieces: the larger C3c fragment corresponding to beta(1A) and the smaller C3d fragment to alpha(2D) of aged serum. The c- and the d-fragments were separated and characterized. Isolated C3a rapidly lost its anaphylatoxin activity when treated with small amounts of a partially purified, thermolabile 10S alpha-pseudoglobulin of human serum. The conditions of inactivation suggested an enzymatic reaction. The anaphylatoxin inactivator also destroyed the activity of C5-derived anaphylatoxin and of lysyl bradykinin.

Anaphylaxis↗
PubMed1969

Immunological induction of increased vascular permeability. I. A rabbit passive cutaneous anaphylactic reaction requiring complement, platelets, and neutrophils.

Passive cutaneous anaphylaxis (PCA) reactions were produced in rabbits by antibodies to bovine serum albumin. Two types of antibodies were found, each inducing increased vascular permeability, but by means of different mediation systems. One of these antibodies required the presence of complement, platelets, and neutrophils for the induction of the PCA reaction, which was inhibited by antihistamine. This antibody was heat stable, sedimented in the 7S region, and was found in both fast and slow electrophoretic fractions of rabbit gamma-globulin. Homocytotropic antibody was also detected. The PCA reactions induced by this type of antibody did not require platelets or neutrophils and were not inhibited in rabbits depleted of C3 with cobra venom factor. The lesions were, however, prevented by administration of antihistamine.

Animals↗
PubMed1969

Immunological induction of increased vascular permeability. II. Two mechanisms of histamine release from rabbit platelets involving complement.

Two mechanisms have been described whereby rabbit platelets in vitro may be induced to release their contained histamine by the reaction of antigen and antibody. Both processes require the participation of the complement system. In the first, the adherence of platelets to particulate antigens such as zymosan or erythrocytes which have fixed complement through the third component was followed by histamine release. Plasma lacking C6 activity was fully active in this system. In the second mechanism, the reaction of soluble antigen with antibody in the presence of plasma also caused release of histamine from platelets and platelet clumping was observed. The release process, which appeared to follow the adherence of platelets to the immune complex, required the action of C6 and perhaps the later-acting components. No evidence could be obtained that a soluble factor was produced which caused the release. Instead, an inhibitor of the release process was detected after incubation of antigen, antibody, and plasma. Antibody preparations capable of giving complement-dependent PCA reactions in rabbits were also shown to induce the release of histamine from platelets in vitro.

Animals↗
PubMed1968

Isolation and characterization of permeability factors from rabbit neutrophils.

Four basic proteins that increase vascular permeability have been isolated in purified form from rabbit neutrophilic granules. These proteins are termed band 1, 2, 3, and 4 protein according to their electrophoretic migration in acrylamide gel. Molecular weights of band 1 and 2 protein derived from amino acid composition were 4800 and 5300, respectively. These values are in good agreement with those obtained for these proteins by gel diffusion techniques. The molecular weight of band 3 protein was also in the range of 5000 by the latter technique. The molecular weight of band 4 protein determined by ultracentrifugal analysis and amino acid composition was 12,000. Although all four proteins had the capacity to induce immediate increase in vascular permeability, only band 2 protein was found to release histamine from isolated rat peritoneal mast cells. Furthermore, it has been shown that the permeability-inducing activity of band 2 protein can be inhibited by pretreating rabbits with antihistamine. Band 2 protein did not release histamine from rabbit platelets and depletion of rabbit platelets from the circulation had no influence on the permeability-inducing activity of this protein. Band 1, 3, and 4 proteins did not release histamine from isolated rat peritoneal mast cells and their capacity to increase vascular permeability remained unaffected by treatment of rabbits with antihistamine. These investigations suggest that the histamine-releasing activity of band 2 protein is a specific phenomenon and is associated with particular amino acid grouping or spacial configuration of the molecules. By the same token, the increase in vascular permeability induced by the nonhistamine-releasing band 1, 3, and 4 proteins represents a specific phenomenon (or phenomena) not particularly related to the over-all charge of these molecules.

Acrylates↗
PubMed1968

The derivation of two distinct anaphylatoxin activities from the third and fifth components of human complement.

Anaphylatoxin activity was derived from both human C'5 and C'3 molecules. This was achieved in the case of C'5 by interaction with trypsin or with EAC'4, (oxy)2a, 3. The smooth muscle-contracting material obtained from the treated C'5 was found to be a fragment of approximately 9,000-11,000 molecular weight. Its action was inhibited with antihistamine. The trypsinized C'5 also increased vascular permeability in guinea pig skin. When human C'3 was incubated with C'3 inactivator complex, which consists of a cobra venom protein and a beta-globulin of human serum, anaphylatoxin activity was observed. The activity was associated with a fragment cleaved from the C'3 molecule, having a molecular weight of between 6,000 and 15,000 as determined by gel filtration techniques. Similar activity was derived from C'3 by the C'3-converting enzyme in free or in cell-bound form. The C'5 anaphylatoxin failed to cross-desensitize guinea pig ileum to the contracting capacities of C'3 and guinea pig anaphylatoxin and vice versa. Anaphylatoxin prepared from C'3 by all methods mentioned above caused cross-desensitization to the other C'3 derivatives, but failed to desensitize to guinea pig anaphylatoxin.

Anaphylaxis↗
PubMed1968

The localization of circulating immune complexes in experimental serum sickness. The role of vasoactive amines and hydrodynamic forces.

In serum sickness, mechanisms by which circulating immune complexes become localized in the walls of vessels and glomeruli have been studied. In affected arteries, morphologic observations showed that circulating marker particles of carbon would rapidly deposit along the luminal surface of the internal elastic lamina. This, as in previous studies, suggested an increase in vascular permeability during which large molecules were capable of being trapped by a filtering membrane in the vessel wall. In attempts to prevent the increase in vascular permeability, rabbits were treated with antagonists of histamine and serotonin. Such treatment markedly inhibited the localization of immune complexes in glomeruli, the development of proteinuria, and glomerular endothelial proliferation. Cardiovascular lesions also were largely prevented from developing. Depletion of platelets, the principal reservoir of vasoactive amines, had a similar though less pronounced effect. While the deposition of immune complexes was inhibited, allergic inflammation in general was not, since normal rabbits treated as above were found capable of developing full Arthus reactions and acute nephrotoxic nephritis. Hydrodynamic factors were noted to be important in determining the location of arterial lesions. Studies of aortas from unmodified rabbits and from those with surgically induced coarctations of the abdominal aorta revealed intimal lesions concentrated at areas of high turbulence, such as at branches, bifurcations, outflows and zones of configurational change. Lesions in these areas were also largely inhibitable by depletion of platelets or by antagonists of histamine and serotonin.

Animals↗
PubMed1968

Studies on circulating immune complexes. 3. Factors governing the ability of circulating complexes to localize in blood vessels.

The relationship between certain physicochemical properties of circulating immune complexes and their ability to localize in vessel walls during a state of increased permeability was studied. The ability to become deposited was related to the large size of complexes, rather than to their net charge or to a specific affinity between complexes and structures of vessel walls. Soluble complexes with sedimentation rates greater than 19S were capable of being entrapped along the vessel wall membranes, while complexes smaller than this were not. These large complexes were removed rapidly from the circulation, while smaller complexes persisted. Minimal levels of total complexes in the circulation necessary for detectable vascular localization were found to be as low as 15 microg antibody N/ml plasma. In experimental serum sickness, a disease known to be induced by circulating immune complexes, the development of vascular and glomerular lesions occurred almost exclusively in rabbits having large (greater than 19S) circulating immune complexes. Animals with smaller complexes did not show deposition of complexes in glomeruli or development of glomerulonephritis. Their incidence of vasculitis was markedly reduced.

Animals↗