Molecular mechanisms involved in the inhibition of neutrophil locomotion by tumor cells.
A chronic myelogenous leukemia cell line (K562) releases a factor of about 8 kD which we have named K562-inhibitory factor (K562-IF) because it inhibits neutrophil locomotion. This factor has potent anti-inflammatory activity in mice, associated with an inhibition of neutrophil function including not only random locomotion and fMetLeuPhe- or serum-induced locomotion but also adherence and zymosan-induced chemiluminescence and degranulation. In contrast, K562-IF does not affect the oxidative burst induced by soluble compounds such as fMetLeuPhe and phorbol esters. Analysis of the mechanism of action of K562-IF on neutrophils showed that it involves an adherence protein, mainly CR3 (the receptor of complement fraction iC3b). Neither, CR3 expression nor its up-regulation were altered, whereas the function of CR3 was depressed, i.e., it failed to cap upon neutrophil stimulation and did not bind iC3b. One unexplained finding is that K562-IF inhibits actin polymerization induced by fMetLeuPhe but not by activation of the Fc-gamma receptor III. Studies are underway to establish whether K562 cells are representative of other malignant cells with regard to the production of neutrophil inhibitors.
Amar
M
M
Laboratoire d'Hématologie et d'Immunologie, CHU Xavier BICHAT, Université Paris 7, France.
Pham Huu
T
T
Amit
N
N
Hakim
J
J
D000818:Animals; D000893:Anti-Inflammatory Agents / Q000494:pharmacology; D001685:Biological Factors / Q000302:isolation & purification / Q000378:metabolism / Q000494:pharmacology*; D002634:Chemotaxis, Leukocyte / Q000187:drug effects*; D006801:Humans; D007249:Inflammation / Q000139:chemically induced / Q000188:drug therapy / Q000473:pathology; D015464:Leukemia, Myelogenous, Chronic, BCR-ABL Positive / Q000473:pathology*; D051379:Mice; D008807:Mice, Inbred BALB C; D009240:N-Formylmethionine Leucyl-Phenylalanine / Q000037:antagonists & inhibitors / Q000494:pharmacology; D009504:Neutrophils / Q000187:drug effects* / Q000502:physiology; D010538:Peritonitis / Q000139:chemically induced / Q000473:pathology; D010587:Phagocytosis / Q000187:drug effects; D016897:Respiratory Burst / Q000187:drug effects; D012397:Rosette Formation; D014407:Tumor Cells, Cultured; D015054:Zymosan / Q000633:toxicity
D000893:Anti-Inflammatory Agents; D001685:Biological Factors; D009240:N-Formylmethionine Leucyl-Phenylalanine; D015054:Zymosan