Systemic suppression of human peripheral blood phagocytic leukocytes after whole-body UVB irradiation.

We examined systemic effects of whole-body UVB irradiation on human peripheral blood phagocytes. We found that 24 h after a single erythemal dose of UVB radiation two phagocyte functions, adhesion and phagocytosis, were reduced by 50%. This functional suppression was accompanied by a significant decrease in the expression of complement receptors (CR1 and CR3) and IgG Fc receptors (FcRII and FcRIII). The greatest reduction (47%) was observed in CR3, which is important for both adhesion and phagocytosis. A kinetic analysis showed that both CR1 and CR3 levels started to decrease 15 min after the UVB exposure, reaching the lowest levels at 4.5- and 24-h time points, respectively. The down-modulation of CRs after whole-body UVB exposure was not due to a defective receptor synthesis or translocation from internal stores to plasma membrane because the maximal CR levels in stimulated cells were not affected by UVB. No change in the serum soluble ICAM-1 was detected after UVB, which rules out CD1 1b epitope masking by sICAM-1. UVB did not release low-receptor-density myeloid progenitor cells from storage pools into circulation. Interleukin 10, a mediator of UVB-induced immunosuppression, was unable to modulate CR expression in vitro. When seven suberythemal whole-body UVB exposures were given repeatedly within 2 weeks, a significant decrease in CR expression was seen, which was greatest after three irradiations. Our data suggest that an exposure to UVB has systemic effects in humans which, possibly due to the down-modulation of preexisting cell-surface receptors, suppress some important functions of circulating phagocytic cells.     

Enhanced phagocytic activity of blood leukocytes in athymic nude mice

After 30-min incubation, blood leukocytes of adult athymic BALB/c nude mice (nu/nu) have a distinctly higher methacrylate or yeast particle uptake than leukocytes of euthymic nu/+ or +/+ mice. This permanent enhancement is not due to humoral factors, since the percentage of phagocytosing nu/nu leukocytes increases further in nu/+ littermate's plasma. Also, chronic infection or intraperitoneal immunization causes an additional transitory increase of the percentage of phagocytosing leukocytes and numbers of particles ingested; the phagocytic performance of leukocytes of euthymic mice is raised under these conditions by a greater factor. In fetuses enhanced phagocytosis of nu/nu mice is found only in monocytes. The bulk of ingestion of methacrylate particles is mediated by Fc receptors and significantly more receptors for IgG2B, IgG1, and IgG2A are demonstrable on nu/nu neutrophils; ingestion of particles via these receptors is again higher in nu/nu neutrophils, whereas nu/nu monocytes display a higher uptake via Fc(IgG1) receptors.     

IgG4 and release of histamine from human peripheral blood leukocytes

Allergen-specific IgG4 was found in the sera from many normal, nonallergic individuals. Basophil leukocytes from donors with IgG4 antibodies to an allergen, but without IgE antibodies to the same allergen, did not release histamine when challenged with this allergen. In some cases, anti-IgG4 antiserum induced a release of histamine from the leukocytes. However, these cells also release histamine after incubation with normal rabbit serum or normal sheep serum. It is concluded that the IgG4-RAST cannot be used for the detection of IgG short-term sensitizing antibodies.     

Histamine release from human peripheral blood leukocytes analyzed by histamine radioimmunoassay

Histamine release from human peripheral blood leukocytes, afterin vitro challenge with allergen extracts, is usually measured by fluorometry. In the present study we compared the results of the automated fluorometric histamine assay (Siraganian) with those of the Immunotech histamine radioimmunoassay. Histamine release dose — response curves obtained after histamine measurement by both methods were superimposable.     

Spontaneous DNA damage in peripheral blood leukocytes from donors of different age

Spontaneous DNA damage in peripheral blood cells was studied in healthy donors of different age (23–70 years). Alkaline comet assay was used to evaluate total DNA damage in individual cells. The individual variability in venous blood samples was higher than in capillary blood samples. The advantage of analysis of DNA damage in nucleated cells from the whole blood is more preferable compared to experiments with isolated lymphocytes because all cell populations in the sample are analyzed. Study of blood cells from healthy donors showed that the mean percent of DNA in the comet tail tended to decrease with age. However, correlation analysis revealed no relationship was found between donor age and degree of spontaneous DNA damage. __________ Translated from Byulleten’ Eksperimental’noi Biologii i Meditsiny, Vol. 145, No. 2, pp. 154–157, February, 2008     

Evaluation of apoptotic leukocytes in peripheral blood smears

OBJECTIVES: Apoptosis is a phenomenon of physiological cell death in which each step is regulated, similar to the process of mitosis. We observed apoptosis in leukocytes during the review of peripheral blood smears. This study was undertaken to evaluate the morphologic features of apoptotic leukocytes in peripheral blood smears and to ascertain their clinical significance. DESIGN: Sixty cases (23 males and 37 females, aged newborn to 92 years) exhibiting apoptotic leukocytes in peripheral blood smears were studied. Medical records for each case were reviewed, and patients were categorized according to their clinical diagnoses. RESULTS: Neutrophils were the most common apoptotic leukocytes identified (85%), followed by lymphocytes (18%) and eosinophils (2%). The diagnosis most frequently associated with the presence of apoptotic leukocytes was infection (55%). Apoptosis in lymphocytes was comparatively less common, but when present, the most common associations were diabetes mellitus, glucocorticoid administration, and neoplastic diseases. CONCLUSIONS: Our findings suggest that the presence of apoptotic leukocytes in peripheral blood smears may help in the differential diagnosis and may be related to the severity of disease. We recommend further evaluation using additional special techniques for detecting apoptotic leukocytes.     

Microsatellite instability in the peripheral blood leukocytes of HNPCC patients

Most hereditary nonpolyposis colorectal cancer (HNPCC) patients inherit a defective allele of a mismatch repair (MMR) gene, usually MLH1 or MSH2, resulting in high levels of microsatellite instability (MSI‐H) in the tumors. Presence of MSI in the normal tissues of mutation carriers has been controversial. Here we directly compare MSI in the peripheral blood leukocyte (PBL) DNA of seven HNPCC patients carrying different types of pathogenic MMR mutations in MLH1 and MSH2 genes with the PBL DNA of normal age‐matched controls and of patients with sporadic colorectal cancer (SCRC). Small pool PCR (SP‐PCR) was used studying three microsatellite loci for at least 100 alleles each in most samples. The average frequencies of mutant microsatellite fragments in each HNPCC patient (0.04–0.24) were significantly higher (p<0.01) relative to their age‐matched normal controls with mutant frequencies (MF) from 0.00 to 0.06, or SCRC patients (MF from 0.01–0.03). The data support the conclusions that higher MF in the PBL DNA of HNPCC patients is real and reproducible, may vary in extent according to the type of germline MMR mutation and the age of the individual, and provide a possible genetic explanation for anticipation in HNPCC families. Hum Mutat 31:317–324, 2010. © 2010 Wiley‐Liss, Inc.