Biological Activity of Complement in Vivo

Abstract

The development of quantitative in vitro methods for the analysis of various mediators of the inflammatory response has led to a greater understanding of the functions of such mediators. Indeed, recent investigations have suggested that the complement (C) ~ system plays a central role as an effector of a number of events in the inflammatory process (1, 2). A point which has emerged from various in vitro studies, however, is that there are a multiplicity of mediators for any given biological function. For example, fragmentation products from each of the complement, clotting, and kinin systems have been reported to increase vascular permeability, contract smooth muscle, and chemotactically attract polymorphonuclear leukocytes (PMN) (3). Important questions for future investigations will be aimed at determining the relative quantitative and qualitative importance in vivo of each of the known biological effectors in mediating any given aspect of the inflammatory process.A cardinal event in the acute inflammatory response is the accumulation of PMN at the inflammatory site. While we have previously discussed the importance of the fifth component of C (C5) in the generation of PMN, as well as mononuclear leukocyte chemotactic activity in vitro (4, 5), information on the role C5 plays in mediating the local accumulation of leukocytes in vivo is quite sparse. In this report, data will be presented which suggest an important role for C5 in the early accumulation of PMN in inflammatory exudates. Materials and MethodsAnimals.--Hartley-strain albino male guinea pigs were obtained from the Animll Resources Branch of the National Institutes of Health. Male mice of the lines B10D2/SN "new" (C5-normal) and B10D2/SN "old" (C5-deficient) (6) were purchased from Jackson Laboratories, Bar Harbor, Maine.Inflammatory Stimulants.--SheUfish glycogen (Mann Research Labs. Inc., New York) was used at a final concentration of 0.5% (w/v) in pyrogen-free saline. Endotoxin derived from I Abbreviations used in this paper: BSA, bovine serum albumin; C, complement; CS-deficient, B10D2/SN "old"; C5-normal, B10D2/SN "new"; GVB, gelatin Veron~l buffer; PBS, phosphate-buffered saline; PMN, polymorphonuclear leukocytes.

Escherichia Coli Bacteremia in the Squirrel Monkey I. EFFECT OF COBRA VENOM FACTOR TREATMENT

“…CoF treatment had no influence on the endotoxin-induced neutropenia of the Shwartzman reaction in rabbits but events during the first 4 h postinjection were not reported (16). The accumulation of neutrophils in inflammatory exudates following i.p endotoxin administration was markedly retarded in C5-deficient mice (55). In the studies reported here, CoF-treated monkeys required 20-30 times longer to develop maximal neutropenia after bacterial challenge than did control animals.…”

Impaired Chemotaxigenesis by Type III Group B Streptococci in Neonatal Sera: Relationship to Diminished Concentration of Specific Anticapsular Antibody and Abnormalities of Serum Complement

“…Our studies demonstrate that serum complement-derived peptides (C5a and C5a des-arg) (12,18,42) account for the majority of chemotactic activity derived from GBS-serum interactions, and that chemotactic factors elaborated by GBS independent of serum are quantitatively of less overall importance. These findings are in accord with observations previously reported for other bacterial pathogens (24,48,49).…”

Experimental Gingivitis in the Albino Hamster

“…Bacteria or their products may' directly damage periodontal tissues, however, it is likely that the inflammatory process of periodontal disease is a result of the interaction between bacterial products and the host's immune system (Bahn, 1970 (Snyderman, Phillips, and Mergenhagen, 1971). These mediators include histamine, serotonin, and bradykinin.…”