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Biomedical subjects

R Snyderman

Publications and source records attributed to R Snyderman.

At least 253 records · Page 14Linked to original sources

Neutralization of sensitized virus by the fourth component of complement.

Herpes simplex virus which had been sensitized with IgM antibody was not neutralized by the addition of the purified activated first component of complement. In the presence of an optimum concentration of the first component of complement, however, the sensitized virus was neutralized by the addition of a high concentration of the purified fourth component of complement. Under these conditions, the addition of the purified second and third components of complement failed to enhance virus neutralization. With low concentrations of the fourth component of complement, the addition of the second and third components enhanced virus neutralization.

Animals↗

Chemotactic and anaphylatoxic fragment cleaved from the fifth component of guinea pig complement.

The fifth component of guinea pig complement, with a sedimentation coefficient 7.8S, is cleaved by sensitized sheep erythrocytes treated with the first four components of complement into two fragments with sedimentation coefficients of 7.4S and 1.5S. The smaller fragment, with a molecular weight of about 15,000, possesses chemotactic activity for rabbit polymorphonuclear leukocytes, as well as anaphylatoxic activity for guinea pig ileum.

Anaphylaxis↗

Interactions of the complement system with endotoxic lipopolysaccharide. Generation of a factor chemotactic for polymorphonuclear leukocytes.

Endotoxic lipopolysaccharide has recently been shown to fix large amounts of the complement components related to the biologic activities mediated by that system. The present study sought to determine whether the generation of chemotactic factor by endotoxin in serum was dependent upon complement system activation. Preheating serum, incubating at 0 degrees C, or incubating in the presence of EDTA, all prevented chemotactic factor generation as well as complement fixation by endotoxin. "Endotoxoids" deficient in complement-firing activity were also deficient in chemotactic factor generation. Chemotactic factor could not be generated by endotoxin in sera of mice congenitally deficient in the C'S component of complement, while chemotactic factor was generated by endotoxin in the sera of coisogenic mice with normal complement levels for that species. The chemotactic factor induced by endotoxin was heat stable and nondialyzable. Molecular sieve chromatography and sucrose density gradient ultracentrifugation demonstrated that the chemotactic factor was a relatively low molecular weight product (15,000-30,000) and as such different from previously scribed C' system-derived chemotactic factors. These experiments demonstrate that generation of chemotactic factor by endotoxin in serum is dependent upon C' system activation involving at least C'5. Furthermore, the relatively low molecular weight of this factor suggests that it might be derived from activation of a single complement component rather than from complexing of multiple complement components.

Animals↗

Regulatory mechanisms of a chemoattractant receptor on human polymorphonuclear leukocytes.

The oligopeptide chemotactic factor receptor in leukocyte membranes exists in two affinity states that are in part interconvertible. Convertibility is regulated by guanine nucleotides, which suggests that a nucleotide regulatory unit allosterically modifies receptor affinity and participates in its transduction mechanisms. Approximately one-third of the high-affinity receptors in polymorphonuclear leukocyte (PMN) membranes are not subject to guanine nucleotide regulation. This fraction can be increased by agonist preincubation and could represent an intermediate form of the receptor prior to signal transduction and/or internalization. Pharmacologic manipulation of viable PMNs demonstrates that the affinity and functional activity of the chemoattractant receptor can be altered divergently by aliphatic alcohols and polyene antibiotics. The alcohols raise the receptors' affinity, enhance chemotaxis, but markedly depress chemoattractant-induced secretory mechanisms. In contrast, polyene antibiotics lower the receptors' affinity, depress chemotaxis, but enhance specific granule secretion. Thus, a relationship exists between the chemoattractant receptors' affinity and their ability to transduce signals for either chemotaxis or secretion.

Alcohols↗

Leukocyte activation by chemoattractant receptors: roles of a guanine nucleotide regulatory protein and polyphosphoinositide metabolism.

Chemoattractant receptors on leukocytes are coupled to a guanine nucleotide regulatory (N or G) protein that stimulates a membrane-associated phospholipase C to hydrolyze phosphatidylinositol 4,5-biphosphate. The products of this hydrolysis are inositol 1,4,5-trisphosphate and 1,2-diacylglycerol, which act as second messengers by raising intracellular levels of Ca++ and activating protein kinase C, respectively. These processes promote cellular activation but also initiate reactions that feed back to inhibit the stimulatory pathway.

Animals↗