Modulation of alloreactivity by Mac-1+, -2+, and -3+ macrophages from normal and tumor-bearing hosts: flow cytofluorometrically separated macrophages.

Abstract

Macrophages (M phi) are multifunctional cells that regulate humoral and cellular immune responses. Our studies of tumor-induced M phi-mediated dysfunction used M phi subsets which were defined by their Mac-1, Mac-2, and Mac-3 surface markers. To measure the accessory activity of M phi for T cell alloreactivity, thioglycollate-elicited peritoneal M phi from normal and tumor-bearing hosts (TBH) were labeled with anti-Mac-1, -2, or -3 antibodies and separated by flow cytofluorometry. The separated Mac-1+, -2+, and -3+ M phi were called sorted M phi, while unseparated M phi were designated unsorted M phi. Both M phi types were added to mixed lymphocyte reaction (MLR) cultures at concentrations ranging from a low of 2% M phi to a high of 20% M phi. The low concentration of unsorted normal host M phi caused a 31% suppression of alloreactivity. Suppression reached 68% when high concentrations of unsorted normal host M phi were added to the MLR cultures. Unsorted TBH M phi reduced alloreactivity by 64% and 86% at low and high concentrations, respectively. When separated into subpopulations, normal host Mac-1+ M phi reduced alloreactivity by 48% and 81% when added at low and high concentrations, respectively. TBH Mac-1+ reduced alloreactivity by 31% and 59% at low and high concentrations, respectively. There were no differences in the suppression caused by normal or TBH Mac-2+ M phi, and by normal or TBH Mac-3+ M phi. Indomethacin treatment did not effect the suppression caused by Mac-1+ M phi, suggesting that proataglandin E2 was not involved. Indomethacin treatment did reduce suppression mediated by Mac-2+, -3+, and unsorted M phi. Mac-2+ M phi dramatically enhanced alloreactivity at low concentrations with normal host Mac-2+ M phi providing greater enhancement of alloreactivity than TBH Mac-2+ M phi. The division of M phi into subpopulations on the basis of Mac antigens suggested that Mac-1+ and -3+ M phi played a major role in immunosuppression in the normal host, while Mac-3+ M phi were more active in TBH immunosuppression. Because no one population of sorted TBH M phi was more suppressive than sorted normal host M phi, we suggest that tumor-induced immunosuppression may involve a network of suppressor M phi.

• Authors: D Askew, C J Burger, K D Elgert
• Journal: Immunobiology (Immunobiology) Vol. 182 Issue 1 Pg. 1-10 (Dec 1990) ISSN: 0171-2985 [Print] Netherlands
• PMID: 2151512 (Publication Type: Journal Article)

Chemical References

• Antigens, Differentiation
• Galectin 3
• Isoantigens
• Macrophage-1 Antigen
• Thioglycolates
• monocyte-macrophage differentiation antigen
• Indomethacin

Topics

• Animals
• Antigens, Differentiation (immunology)
• Fibrosarcoma (chemically induced, immunology)
• Flow Cytometry
• Fluorescent Antibody Technique
• Galectin 3
• Immune Tolerance
• Indomethacin (pharmacology)
• Isoantigens
• Lymphocyte Culture Test, Mixed
• Macrophage-1 Antigen (immunology)
• Macrophages (immunology)
• Male
• Mice
• Mice, Inbred BALB C
• Peritoneal Cavity (cytology)
• Spleen (immunology)
• Thioglycolates