Wound-induced alterations in survival of 60Co irradiated mice: importance of wound timing.

Wounding mice shortly before or shortly after lethal 60Co irradiation enhances survival. Survival of wounded-irradiated mice may be due to enhanced hematopoietic recovery as measured by endogenous spleen colony (E-CFU-s) formation.

Hematopoietic colony-forming cells from mice after wound trauma.

The changes produced in the pluripotential and progenitor cell compartments of the hind leg bone marrow and spleen of skin-wounded mice were examined over a 2-week post-trauma period. Pluripotent cells (colony-forming unit-spleen, CFU-s) were significantly increased in the spleen and slightly reduced in the leg marrow the first week after trauma. Granulocyte macrophage colony-forming cells (GM-CFC) were significantly increased in the spleen throughout the 2-week period and were increased in the leg marrow during the first post-trauma week. Macrophage colony-forming cells (M-CFC) were significantly decreased in the spleen during the 2-week period and were slightly elevated in the leg marrow during that time. The peripheral blood contained significantly increased concentrations of CFU-s and GM-CFC but not M-CFC. Serum of wounded mice supported growth of GM-CFC but not M-CFC. The growth-promoting factor was extractable by CHCl3 treatment. Serum C-reactive protein concentrations were significantly increased for a 5-day period after wound trauma.

Modulations in mouse hemopoiesis after engraftment with Lewis lung (3LL) carcinoma cells.

Hemopoietic changes in male C57BL/6Cum BR mice engrafted with Lewis lung carcinoma (3LL) were evaluated between day 7, when palpable tumors were present, to day 30 postengraftment. All experimental animals demonstrated decreasing hematocrits (down 40% by day 30) with concurrent leukocytosis which by day 30 postengraftment had reached levels 13.4 times normal. The myelocytic/erythrocytic ratio for normal animals was 1:3 (bone marrow: spleen). The ratio for engrafted animals ranged between 10:1 and 40:1. This apparent shift in production priorities is even more significant in light of the fact that femoral bone marrow cellularity had decreased by 33% on day 17. Splenomegaly, evident by day 7, was seven times control by day 17. Clonogenic analysis of erythroprogenitor cell concentrations revealed an inverse relationship between bone marrow and spleen. 27 days after engraftment, splenic populations demonstrated significant increases in colony forming unit-erythroid (115-fold), burst forming unit-erythroid (7.4-fold), whereas bone marrow concentrations had decreased (6-fold). This report suggests that initiation of 3LL tumor in mice results in a change in the degree of hematopoietic priorities and participation of erythroid organs.

Skin wound-enhanced survival and myelocytopoiesis in mice after whole-body irradiation.

Skin wounding at 24 h before whole-body 60Co irradiation of mice raised the LD50/30 from 8.09 to 9.71 Gy resulting in a dose reduction factor of 1.2. Concentrations and quantities of myeloproliferative cells were examined at 3, 7, 10, and 14 days after 7 Gy, skin wounding 24 h before 7 Gy and in control non-treated mice. Wounding before irradiation provoked an increase in marrow and splenic clonogenic cells that was earlier and greater than that noted for irradiated mice. Supranormal levels of splenic CFu-s and CFU-c were found in animals wounded before irradiation. M-CFC values were depressed throughout, although greater for combined injured animals than for irradiated mice.

Proliferative responses of lympho-myelopoietic cells of mice after wound trauma.

The hypothesis that wound trauma produces either selective or total organ cell population alterations in the quantities of lympho-myeloproliferative elements in the major hematocytopoietic centers was tested. Mice were subjected to a 4% body surface skin wound on the anterior dorsum; their tissues were assayed 24 hours later for their total cellularity and proliferative potential. In wounded mice, the marrow cellularity was significantly decreased but this did not result in lower stem cell (CFU-s) and progenitor cell (CFU-c and M-CFC) quantities. However, there were significant selective and total population reductions in cells responsive to T and B cell mitogens. Splenic cellularity and stem cell quantities in wounded mice did not differ from control-treated animals. However, there were both selective and total population reductions in splenic CFU-c and M-CFC. Wounding resulted in a greater splenic T cell response to phytohemagglutinin PHA, while the responses to concanavalin-A (CON-A) were similar to controls. The splenic B lymphocyte population was specifically increased. Wounding resulted in a significant thymic hypocellularity. This was mirrored by a selective decrease in M-CFC and a total cell population reduction in response to T cell mitogens.