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.
Laboratoire d'Hématologie et d'Immunologie, CHU Xavier BICHAT, Université Paris 7, France.
M
M
Amar
T
T
Pham Huu
N
N
Amit
J
J
Hakim
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