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J K Phillips

Publications and source records attributed to J K Phillips.

39 records · Page 3Linked to original sources
PubMed1971

Biological activity of complement in vivo. Role of C5 in the accumulation of polymorphonuclear leukocytes in inflammatory exudates.

The importance of C5 in the generation of complement (C)-dependent chemotactic activity in vitro is well recognized. However, the actual role C5 may play in the accumulation of polymorphonuclear leukocytes (PMN) at inflammatory sites in vivo has not been established. Injection of glycogen or endotoxin into the peritoneal cavities of guinea pigs resulted, shortly thereafter, in the local accumulation of PMN. Preceding the influx of leukocytes, the peritoneal fluid became chemotactic for rabbit PMN in vitro. The majority of this activity could be attributed to a cleavage product of C5 (C5a). Similarly, injection of endotoxin into the peritoneal cavity of C5-normal mice resulted in the generation of a chemotactic factor for mouse PMN which was followed by the accumulation of PMN in the peritoneal fluid. In contrast, injection of endotoxin into the peritoneal cavity of C5-deficient mice resulted in the generation of virtually no detectable chemotactic activity and a markedly depressed accumulation of PMN during the first 24 hr after injection. The data suggest that C5 plays an important role in the early phases of PMN accumulation in response to inflammatory stimuli. The rapid accumulation of PMN in response to an inflammatory stimulus such as bacterial endotoxin would be expected to be a major factor in host defense against proliferation and dissemination of infectious agents.

Animals↗
PubMed1968

Interactions of the complement system with native and chemically modified endotoxins.

Endotoxic lipopolysaccharides (LPS) isolated from Serratia marcescens, Veillonella alcalescens, and Salmonella typhosa were potent in their ability to induce fixation of complement (C') in normal guinea pig, rabbit, mouse, and human serum. The C'-fixing ability of LPS was pronounced even when assays were performed in undiluted serum, and was lost after each of four chemical modifications which resulted in loss of biological toxicities. The detoxification procedures had in common the cleavage of ester-bound, long-chain carboxylic acids. The ability of biologically active LPS to fix C' in normal guinea pig serum was reflected chiefly in dramatic uptake of classical C'3 (C'3t); fixation of C'1, C'4, and C'2 was virtually undetectable. Hence, it was the capacity for fixation of C'3t which was lost most overtly during detoxification. Addition of immune serum to the assay mixtures resulted in detectable fixation of C'1 and C'4. Biologically active LPS also fixed more of these components than did detoxified LPS. Immune serum restored the ability of detoxified LPS to fix C'3t, but whether this is by the original pathway is not yet clear. We concluded that the loss of certain biological activities and the loss of ability to fix C'3t in normal serum after LPS detoxification involved loss or rearrangement of substrates on LPS which either initiated or supported, or both, its interaction with the complement system. It was apparent that the ability to fix C' can serve as a valuable in vitro indicator of the integrity of the toxic conformation of biologically active LPS membrane fragments. These experiments supported the hypothesis that certain of the biological activities induced by endotoxins are mediated via the complement system.

Animals↗