Inflammation and anti‐tumor resistance. V. Production of a cytostatic factor following cooperation of elicited polymorphonuclear leukocytes and macrophages

Abstract

When Lewis tumor cells (3LL) included in a gel of polyacrylamide microbeads are injected into mice and recovered 1 day later, incorporation of 125I-UdR is strongly reduced. In contrast, no reduction is observed in irradiated mice. The cytostatic effect is non-existent in 6 hr-old granuloma (granulocytes 90%, macrophages 10%), but is maximal in 48 hr-old granuloma (granulocytes 50%, macrophages 50%). When 6 hr-old granuloma cells (which are not cytostatic) are incubated with bone-marrow-derived macrophages (BMs) (which are slightly cytostatic), considerable cytostasis against 3LL is observed, such an effect being strongly reduced if the 2 cell populations are separated. This suggests that close contact of live polymorphs with macrophages is necessary for full expression of cytostasis. No increase in cytostasis of bone-marrow macrophages is observed when BMs are incubated with a cell-free extract of freeze-thawed 6-hr-old granuloma cells. Cell contact is not necessary between granuloma cells and 3LL since the cytostatic activity is found in the supernatant of incubated phagocytic cells. Cytostasis is also observed with B16, P815, J774 cells and normal mouse bone-marrow cells. An active cytostatic fraction has been purified from the supernatant of 48-hr-old granuloma cells following molecular filtration and HPLC. The cytostatic factor has a low molecular weight (400-500 daltons), is not a peptide and presents maximum absorption at 267 nm.

Polymorphonuclear neutrophils and cancer: Intense and sustained neutrophilia as a treatment against solid tumors

“…Later, Takasugi et al showed that peripheral blood PMN possessed nonspecific cytotoxicity against various cultured human tumor lines,17 and Clark et al reported that peroxidase systems present in inflammatory cells,18 and especially the PMN,19 were cytotoxic for mouse lymphoma cells. Over the following years, a large number of reports showed that PMN had cytotoxic and/or cytostatic effects on cancer cells in vitro 20–95. Weiss and Slivka showed that the ability of PMN to destroy human T lymphoblasts was at least the same as that of monocytes,35 and in mice, PMN were found more cytotoxic to several tumors than were macrophages 53.…”

Genetics of chemical carcinogenesis: Analysis of bidirectional selective breeding inducing maximal resistance or maximal susceptibility to 2-stage skin tumorigenesis in the mouse

“…This is a general phenomenon since in lines of mice selected for high or low antibody responsiveness the normal process of multiplication and differentiation of lymphoid tissue was modified with a consequent effect on lymphoma frequency (Covelli et al, 1989). The defense mechanisms developed by the organism against tumorigenesis may be mediated by immunological responses endowed with specificity and memory (Burke and Balkwill, 1996; Klein and Boon, 1993) or non‐specific reactions based essentially in the different forms of inflammation (Hevin et al, 1990; DiGiovanni et al, 1992; Moore et al, 1999).…”

Análise da expressão diferencial dos genes envolvidos na resposta inflamatória aguda e crônica e sua influência na carcinogênese química cutânea em camundongos geneticamente selecionados para alta ou baixa reatividade inflamatória aguda.

“…A eficácia terapêutica de citocinas pró-inflamatórias e hematopoéticas também tem sido demonstrada em animais e pacientes humanos (FIORETTI et al, 1998;HEVIN et al, 1990;SOIFFER et al, 1998 O processo inflamatório inclui liberação de citocinas, fatores de crescimento, polipeptídios quimiotáticos e prostaglandinas, os quais tornaram-se alvos favoritos para prevenção de cânceres de pele induzidos tanto por agentes químicos, quanto por radiação UV (MARKS e FURSTENBERGER, 2000;TRIPP et al, 2003;WILGUS et al, 2003;BOWDEN, 2004). Vários mediadores da inflamação apresentam papéis-chave na carcinogênese cutânea, como: as prostaglandinas, cicloxigenase-2, fator de necrose tumoral-α (TNF-α), AP-1, fator nuclear-κB (NF-κB), transdutor de sinal e ativador de transcrição (Stat) 3 e outros (BUCKMAN et al, 1998;MOORE et al, 1999;SUGANUMA et al, 1999;YOUNG et al, 1999;CHAN et al, 2004;LIND et al, 2004).…”