Microvascular expression of MALA-2 correlates with in in vivo lymphocyte trafficking and is preferentially enhanced in tumors by tumor necrosis factor-α and interleukin-1α

P. A. Dean, P. S. Ramsey, J. H. Donohue, Heidi Nelson

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3 Scopus citations


The role of endothelial cell adhesion molecule expression in the immune response to tumors is unknown. We have investigated the expression of murine lymphocyte activation antigen (MALA-2), the murine equivalent of intercellular adhesion molecule-1 (ICAM-1), in blood vessels of normal murine tissues and in melanoma tumors and evaluated the relationship between MALA-2 expression and lymphocyte trafficking in vivo. C3H/HeN mice were injected both i.p. and s.c. with a clone of K-1735 syngeneic melanoma cells. Day 11 tumor-bearing mice were killed and vascular expression of MALA-2 was quantified using immunohistochemistry. MALA-2 expression was high in lung, liver and spleen and low in lymph node, small bowel, muscle and tumor. Systemic administration of either recombinant tumor necrosis factor α(rTNFα) or recombinant interleukin-1α (rIL-1α) over 2 days poor to organ harvest resulted in an increase in the number of tumor vessels expressing MALA-2, with no change in MALA-2 expression in other tissues. In vivo lymphocyte trafficking was evaluated using cultured, activated splenocytes radiolabeled with 111In. 111In-labeted splenocyte distribution correlated closely with MALA-2 expression, with high localization to spleen, liver and lung and poor localization to lymph node, small bowel, muscle and tumor. Systemic administration of rTNFα, but not rIL-1α resulted in a significant increase in 111In-labeled splenocyte distribution to tumor, but neither rTNFα nor rIL-1α lolaltered 111In-labeled splenocyte distribution to normal organs. Our data demonstrate the in vivo pattern of vascular MALA-2 expression in normal murine tissues and tumors and suggest that the expression of MALA-2 can be preferentially enhanced in tumors by systemic administration of cytokines. Lymphocyte distribution in vivo correlates closely with the pattern of MALA-2 expression, and these data support the conclusion that MALA-2 plays an important role in the regulation of lymphocyte trafficking.

Original languageEnglish (US)
Pages (from-to)639-645
Number of pages7
JournalInternational Journal of Cancer
Issue number5
StatePublished - 1994


ASJC Scopus subject areas

  • Cancer Research
  • Oncology

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