Ectopic hematopoiesis in peritoneal tumor nodules induced by the myeloproliferative sarcoma virus in DBA/2 mice.

Tumor nodules composed of fibroblasts, large undifferentiated cells, granulocytes, and small lymphocytes develop in the spleens of adult DBA/2 mice infected with the myeloproliferative sarcoma virus (MPSV). They spread thereafter in the organism, and at the terminal stage of the disease they are especially numerous on the peritoneal membrane. The present study, performed on those tumor nodules to avoid contamination by exogenous hematopoietic cells, demonstrated that they were sites of granulopoiesis, which may have occurred via the local differentiation of granulomacrophage precursor cells (GM-CFC) and perhaps also from pluripotent hematopoietic stem cells, since these two populations were present in the tumor nodules (25 +/- 11 and 13 +/- 10, respectively, per 5-10(5) cells). Almost all (88%) those GM-CFC were able to clone in vitro without added colony-stimulating factor. A comparative study with the Moloney murine sarcoma virus-induced tumor indicated that the local production of hematopoiesis-stimulating factors was not sufficient to allow such ectopic granulopoiesis. These results imply the presence of a specific hematopoietic microenvironment in the MPSV-induced tumor nodules.

Studies of macrophage function in murine systemic lupus erythematosus. 3. The nature, anatomical location, and reversibility of the phagocytic defect.

The defect in phagocytosis and binding of antibody-coated sheep erythrocytes (EA) by peritoneal macrophages of (NZB X NZW)F1 or B/W mice is not intrinsic, but is related to the development of the autoimmune disease process. The defect appears to be confined to peritoneal macrophages, since bone marrow (BM)-derived macrophages have normal to elevated activities in vitro. The peritoneal macrophage defect is not due to blockade of Fc receptors in vivo, as shown by long-term culture or recovery of phagocytic and binding activities after removal of Fc receptors by pronase, but represents a reduced number of receptors with slightly delayed turnover. The defect can be reversed by elicitation of activated macrophages with Corynebacterium parvum, thioglycollate, or proteose peptone in vivo. Normal Fc-mediated phagocytosis and binding by BM-derived macrophages cultured from untreated autoimmune mice is enhanced by pretreatment of mice with C. parvum, thioglycollate, or proteose peptone. The cause of the defect in Fc-mediated phagocytosis by resident peritoneal macrophages of autoimmune mice was not ascertained; it may be due to abnormal macrophage kinetics or to the local effects of lymphokines released as a result of other autoimmune changes.

Regulation of 1,25-dihydroxyvitamin D3 production by cultured alveolar macrophages from normal human donors and from patients with pulmonary sarcoidosis.

Regulation of the production of the biologically active vitamin D3 sterol 1,25-dihydroxyvitamin D3 [1,25-(OH)2D3] by cultured pulmonary alveolar macrophages (PAM) obtained from 6 patients with pulmonary sarcoidosis and from 9 normal subjects was studied. The sarcoid cells, all collected from patients with normal calcium metabolism, synthesized 1,25-(OH)2-[3H]D3 from the substrate 25-hydroxyvitamin [3H]D3 (25OH-[3H]D3), whereas in vitro incubation with recombinant human interferon-gamma (IFN gamma) or lipopolysaccharide (LPS) was required for induction of synthesis of the hormone by normal PAM. Exogenous 1,25-(OH)2D3 (10-100 nmol/L) decreased endogenous hormone production by normal PAM by approximately 45%. The relative inhibitory effect of 1,25-(OH)2D3 was less pronounced in sarcoid PAM, in which 10-100 nmol/L 1,25-(OH)2D3 inhibited 250HD3-1-hydroxylase by approximately 25%. An accompanying induction of the 250HD3-24-hydroxylase, which is typical for renal cells, was found at low levels in only 3 of 10 experiments; in this regard, no differences between sarcoid and normal PAM were apparent. PTH or forskolin did not influence 250HD3 metabolism by PAM. 1,25-(OH)2D3 production by sarcoid PAM was enhanced by lipopolysaccharide and IFN gamma. Likewise, recombinant human interleukin-2 stimulated 1,25-(OH)2D3 production by sarcoid PAM, suggesting a possible role for both IFN gamma and interleukin-2 in the induction of 1,25-(OH)2D3 synthesis by sarcoid PAM in vivo. Recombinant human IFN alpha, IFN beta, and granulocyte-macrophage colony-stimulating factor had little effect. Dexamethasone and chloroquine, which have in vivo antihypercalcemic activity in sarcoidosis, both inhibited 1,25-(OH)2D3 synthesis by sarcoid PAM; chloroquine simultaneously stimulated the 24-hydroxylase. Our studies suggest that the 250HD3-metabolizing system in PAM is in some respects different from renal metabolism of 250HD3.

Total parenteral nutrition in mice bearing a metastatic carcinoma: tumor growth, metastasis and immunologic parameters.

The role of dietary manipulation of tumor growth, metastasis and immunologic parameters was studied in mice bearing Lewis lung carcinoma. Fourteen days following subcutaneous tumor implant, groups with tumor and their non-tumor bearing counterparts were assigned to one of the following feeding protocols: total parenteral nutrition (TPN), per oral (PO) intake of the parenteral diet, an oral casein diet (CAS), or electrolyte infusion plus the casein diet (ELECT). Intakes of energy and nitrogen were similar among all groups. Mice were killed 12 days later and peritoneal macrophages were tested for phagocytic activity. Tumor growth and metastasis were decreased from both infusion regimens with minimal loss of body weight as compared with casein fed mice. PO mice also showed lower tumor weight but metastasis was as great as in the casein group. Non-tumor-bearing infused mice showed depressed thymic weight, but thymic weight was not further reduced in tumor-bearing infused mice. PO feeding afforded no such protection in the presence of the carcinoma. Splenomegaly was observed in tumor-bearing mice on all regimens, but mice maintained on the parenteral diet demonstrated the largest proportion of macrophages containing nuclear debris. Analysis of free macrophages indicated no effect of diet regimen on non-immune phagocytic activity in both tumor-free and tumor-bearing mice. Possible alteration of splenic macrophage intracellular digestive capacity or phagocytic activity was suggested as a result of TPN.

Hematogenous origin of brain macrophages: a case report.

Del Río-Hortega believed that phagocytic cells in the CNS arise from microglia; however, recent autoradiographic studies have suggested a hematogenous origin for brain macrophages. To clarify this issue, we studied a young man with acute lymphoblastic leukemia and a peripheral white blood cell count of 22/mm3 who had an embolic brain infarct 2 weeks before he died. Macrophages were scarce within the lesion, suggesting that the principal phagocytic cell is hematogenous.

Delayed maturation of skin window macrophages in myelodysplastic syndromes.

Blood monocyte differentiation to macrophages was examined in nine patients with primary myelodysplastic syndromes using the skin window technique. Emigrated cells were stained cytochemically for acid phosphatase reaction after 1, 2, 4, 7, 9, 12 and 23 h. Compared to age-matched controls, seven patients showed a significant delay in lysosomal enzyme acquisition, which is associated with macrophage differentiation. Our results with this in-vivo assay demonstrate an involvement of the monocyte/macrophage system in primary myelodysplastic syndromes and show that patients often have a disturbance in macrophage differentiation.

Effect of hyperthermia on rabbit macrophages.

The effect of water-bath hyperthermia on rabbit peritoneal macrophages was studied in vitro. The cells were exposed to hyperthermia for 30 min to 4 hours and membrane transport of ions as measured by total and ouabain-inhibited 86Rb influx as well as membrane permeability for 86Rb and 51Cr-labelled intracellular proteins were investigated. Heat-treated macrophages were tested for their ability to phagocyte staphylococci and for reduction of nitroblue-tetrazolium. Moreover the effect of microwave whole-body hyperthermia on rabbit phogocytic cells was studied in vivo. Ion transport to macrophages was stimulated by both intensive (43 degrees C) and moderate (40 degrees C) hyperthermia. On the other hand exposition of the cells to 43 degrees C led to pronounced release of 86Rb and 51Cr from prelabelled cells. NBT reduction was generally decreased in macrophages exposed to 43 degrees C and increased in macrophages kept at 40 degrees C. Clearance of 32P-labelled staphylococci from peripheral blood of microwave-irradiated rabbits diminished when animals were exposed to microwave hyperthermia for f or 7 days (2 hours daily).

Cryptogenic abscess of the liver. Evidence of underlying reticuloendothelial cell dysfunction.

Evidence of underlying liver disease and reticuloendothelial system dysfunction was sought in five adults with histories of idiopathic or "cryptogenic" liver abscess. Although no evidence of underlying liver disease was obtained (median follow-up, 3.4 years; range, 2.1 to 4.8 years), four of five individuals demonstrated a marked impairment in their ability to clear antibody-tagged erythrocytes from the systemic circulation. The results of this study suggest that patients who develop cryptogenic abscesses of the liver have an underlying reticuloendothelial cell defect that may predispose them to liver abscess formation.

Studies of macrophage function in murine systemic lupus erythematosus. 4. Failure to reverse the defect in Fc-mediated phagocytosis and binding by in vitro stimulants or prostaglandins.

Previous studies have shown that resident peritoneal macrophages from mice with systemic lupus erythematosus (SLE) show defective Fc-mediated phagocytosis and binding of opsonized sheep erythrocytes (EA) in vitro. Possible causes of this defect in (NZB X NZW)F1 (B/W) mice were investigated. These included a maturational block in peritoneal macrophage differentiation, the production by peritoneal cells of a factor which inhibits Fc receptor expression and phagocytosis, and an abnormal response by macrophages of autoimmune mice to prostaglandins. Resident peritoneal macrophages of B/W mice did not show a maturational block since incubation with either (a) differentiating agents such as 4 beta-phorbol 12 beta-myristate 13 alpha acetate or retinoic acid, or (b) lymphokine (LK), prepared by Con A stimulation of mouse spleen cells, failed to enhance Fc-mediated phagocytosis and binding by B/W cells relative to controls. However, LK from B/W and B6AF1 cells stimulated Fc-mediated phagocytosis and binding by bone-marrow (BM)-derived macrophages of CBA/H mice; B/W LK also stimulated BM cells from B/W mice. Peritoneal cell supernatants did not inhibit phagocytosis of Fc receptor expression by BM-derived macrophages in vitro. Prostaglandin E treatment of peritoneal or BM-derived macrophages in vitro failed to restore decreased phagocytosis and binding of EA induced by culture in indomethacin and failed to stimulate phagocytosis by untreated cultures. The reason for the observed defect remains obscure.

Bone volume and mineral density of iliac crest spongiosa in uremia.

Bone mass and bone mineral content were measured in non-dialyzed and dialyzed uremic patients. Bone mass, measured by micromorphometry and a gas displacement method, was higher in uremic than in age and sex matched control subjects (micromorphometry-U:25.8 +/- 8.24%; Co:15.6 +/- 4.38; gas displacement-U:211 +/- 66 mm3/cm3; Co:191 +/- 45). In hemodialyzed patients, bone mass was lower the longer the patients had been on dialysis (r = 0.38; P 0.05). Bone mineral content (specific weight) was diminished in uremia (1.82 +/- 0.095 g/ml; controls 1.854 +/- 0.0173). In hemodialyzed patients, specific weight was higher, as was Ca content of bone assessed by neutron activation analysis. It is concluded, that negative Ca balance was the major cause of bone loss and that bone loss is thus preventable.

Changes of expression of peritoneal macrophages Fc and C3 receptors induced by transplantable melanomas.

Expression of Fc and C3 receptors was studied in the rosette tests on isolated peritoneal macrophages of control and melanoma-bearing hamsters. In hamsters with transplanted melanomas an increase of the percentage of macrophages with Fc and C3 receptor expression was observed. The increase was prominent among macrophages from animals with transplanted amelanotic melanoma, a tumor line with greater malignancy and changed antigenicity and immunogenicity.

Tobacco smoke and the pulmonary alveolar macrophage.

Our results indicate that tobacco smoke exposure to varying duration causes morphological, biochemical and functional alterations in pulmonary alveolar macrophages. The results of these changes is a population of alveolar macrophages made up of larger cells, with a reduced nucleus-cytoplasmic ratio, which are heavily loaded with heterolysosomes containing lipid. Though their fractional complement of mitochondria remains the same, an increase in the inner mitochondrial membrane surface area may be related to an enhanced oxidative metabolism. The cell is biochemically activated particularly following chronic exposure and is functionally impaired with respect to phagocytosis.

Leukokinesis in bovine ostertagiasis: stimulation of leukocyte migration by Ostertagia.

A blind-well chemotaxis chamber method was used to indicate migration stimulation of bovine neutrophil and eosinophil polymorphonuclear leukocytes and macrophages as related to ostertagiasis. Live exsheathed Ostertagia ostertagi 3rd-stage larvae (L3) and soluble L3 antigen (SLA), prepared by freeze thawing and sonic disruption of L3, enhanced cellular migration for eosinophils, but not for neutrophils and macrophages. Products of lymphocytes cultured with SLA for 3 to 6 hours were also examined, using lymphocytes from peripheral blood of helminth-free cattle and cattle infected with O ostertagi or Trichostrongylus axei. Lymphokines that enhanced cellular migration of neutrophils, eosinophils, and macrophages were present in culture supernatants of SLA-stimulated lymphocytes from O ostertagi-infected cattle, but not from cattle infected with T axei or helminth-free cattle. Seemingly, L3 and SLA were stimulants of eosinophil migration. Further, neutrophil, eosinophil, and macrophage migration was modulated by lymphokines produced by SLA-stimulated lymphocytes from cattle with ostertagiasis.