Elsevier

Molecular Immunology

Volume 17, Issue 2, February 1980, Pages 151-161
Molecular Immunology

Human C5a and C5a analogs as probes of the neutrophil C5a receptor

https://doi.org/10.1016/0161-5890(80)90067-XGet rights and content

Abstract

Quantitative assessment of the human neutrophil chemotactic response and immunologic evidence demonstrate that human C5a and/or its physiological equivalent, C5ades Arg' serves as the predominant chemotactic factor in complement activated serum. Both C5a and its des Arg74 derivative are capable of promoting directed cellular migration as well as lysosomal enzyme release. When neutrophil chemotaxis is assessed by an ‘under agarose methodology’, in the absence of extraneous human serum proteins. C5a is found to be some 10- to 30-fold more active than C5ades Arg Quantitatively similar results are obtained when each factor is assessed for its ability to promote secretion of azurophilic granular enzymes from cytochalasin B-treated neutrophils. The C5a structural analog C5a-(1–69), lacking five residues of the C-terminal portion of the parent molecule, and a synthetic pentapeptide l-methionyl-l-glutaminyl-l-leucylglycyl-l-arginine, which mimics the C-terminal linear sequence of C5a (Chenoweth et al., 1979a), are found to be devoid of biological activity when examined either-alone or in combination. These findings imply that the C-terminal portions of C5a contribute importantly to modulating ligand-receptor interactions on neutrophils. Based on these observations, a conceptual model of the interaction of human C5a with the neutrophil C5a receptor is proposed. We hypothesize that C5a possesses an internal ‘recognition’ site in addition to the ‘activation’ site contained in the C-terminal region of the molecule.

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    This is publication number 1800 from the Research Institute of Scripps Clinic. This work was supported by USPHS grant HL 20220, program project grants HL 16411,1 S07 RR-05514 and a grant from the Council for Tobacco Research (No. CTR 1105). Dr. Chenoweth was supported in part by USPHS grant GM 02179.

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