Defective polymorphonuclear leukocyte formyl peptide receptor(s) in juvenile periodontitis.
Juvenile periodontitis (JP) is a disease characterized by severe gingival infections. PMN from some JP patients exhibit abnormal chemotactic responsiveness when challenged with the synthetic formyl peptide, FMLP. While investigating PMN function in JP, we found a patient in whom abnormal PMN chemotactic responses to FMLP were associated with a defective population of PMN formyl peptide receptor(s) (FPR). JP PMN failed to respond chemotactically when challenged with FMLP, but exhibited normal chemotactic responses upon exposure to purified human C5a. Furthermore, JP PMN were capable of degranulating and generating superoxide anion radicals as well as normal PMN upon exposure to FMLP. Binding studies demonstrated that JP PMN had a diminution in the number of high-affinity FPR. Studies in which FPR was radiolabeled by chemical cross-linking demonstrated that JP PMN FPR exhibited the same molecular weight and N-linked glycosylation as normal PMN FPR. JP PMN FPR, however, was more resistant to papain cleavage than normal PMN FPR. Autoradiograms obtained from 2D-PAGE of normal and JP PMN FPR demonstrated decreased amounts of FPR isoforms in JP PMN.
Perez
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HD
Rosalind Russell Arthritis Research Laboratory, Department of Medicine, University of California, San Francisco 94143.
Kelly
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E
Elfman
F
F
Armitage
G
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Winkler
J
J
D000328:Adult; D000345:Affinity Labels; D010520:Aggressive Periodontitis / Q000503:physiopathology*; D015550:Cell Degranulation / Q000187:drug effects; D002634:Chemotaxis, Leukocyte; D015936:Complement C5a / Q000494:pharmacology; D015180:Electrophoresis, Gel, Two-Dimensional; D005260:Female; D006801:Humans; D008297:Male; D009240:N-Formylmethionine Leucyl-Phenylalanine / Q000378:metabolism* / Q000494:pharmacology; D009504:Neutrophils / Q000502:physiology*; D010449:Peptide Mapping; D044042:Receptors, Formyl Peptide; D011971:Receptors, Immunologic / Q000737:chemistry / Q000502:physiology*
D000345:Affinity Labels; D044042:Receptors, Formyl Peptide; D011971:Receptors, Immunologic; D009240:N-Formylmethionine Leucyl-Phenylalanine; D015936:Complement C5a