Generation of neutrophil-chemoattractant by degradation of tumor cell membrane protein.
Polymorphonuclear leukocytes (PMN) infiltrating into tumors are assumed to be the result of a migration in response to a tumor-derived chemotactic factor. It is hypothesized that tumor-derived chemotactic factors, which are supposed to be in aggregates, can be exposed by proteolytic degradation of the tumor cell membrane protein (TCM). The TCM suspension made from either Sarcoma 180 or Ehrlich ascites tumor after incubation with Varidase at 37 degrees C for six to eight weeks is referred to as a degraded TCM protein (DTCM). The purpose of this study was to detect whether or not the DTCM was chemotactic for PMNs. Chemotactic activity was assayed by a sponge-matrix model and expressed in the number of PMNs infiltrating into the sponge per mouse after intrasponge injection of the DTCM, dose range, 0.4-0.005 mL. Maximal response to DTCM was restricted to the limited dose between 0.01 and 0.02 mL. Quantities of DTCM > 0.02 mL caused a response in roughly reciprocal proportion to the dose of DTCM. Changes in the circulating leukocyte count in response to an intravenous (i.v.) injection of DTCM was biphasic. The initial relative leukopenia was followed by leukocytosis within 24 hours in rats surviving the effect of DTCM doses < 0.5 mL. However, in rats with i.v. injections of higher doses, profound leukopenia was present at death. The mice, after an intraperitoneal (i.p.) injection of DTCM, dose range, 0.5-1.0 mL, died between 16 and 24 hours after the injection. The bone marrow of these mice showed complete depletion of PMNs.(ABSTRACT TRUNCATED AT 250 WORDS)
Hsu
K Y
KY
Department of Surgery, National Taiwan University, College of Medicine, Taipei, R.O.C.
Hsu
S T
ST
Hsu
S Y
SY
D000818:Animals; D001853:Bone Marrow / Q000187:drug effects; D002286:Carcinoma, Ehrlich Tumor / Q000378:metabolism / Q000473:pathology; D002630:Chemotactic Factors / Q000096:biosynthesis* / Q000494:pharmacology; D007958:Leukocyte Count; D008168:Lung / Q000187:drug effects / Q000473:pathology; D008565:Membrane Proteins / Q000378:metabolism*; D051379:Mice; D008813:Mice, Inbred ICR; D009363:Neoplasm Proteins / Q000378:metabolism*; D009504:Neutrophils / Q000187:drug effects* / Q000276:immunology; D051381:Rats; D012513:Sarcoma, Experimental / Q000378:metabolism / Q000473:pathology
D002630:Chemotactic Factors; D008565:Membrane Proteins; D009363:Neoplasm Proteins