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Studies on the leukocytosis and lymphocytosis induced by Bordetella pertussis. 3. The distribution of transfused lymphocytes in pertussis-treated and normal mice.

Peripheral blood lymphocytes were isolated from normal mice and mice undergoing pertussis-induced lymphocytosis. After labeling in vitro with tritiated uridine the cells were transfused into normal or pertussis-treated mice. It was found that the lymphocytes from pertussis-treated mice entered the lymph nodes of both normal mice and pertussis-treated mice to a significantly lesser extent than did normal lymphocytes which had been transfused into either class of recipient. In addition, an interdependence of changes in the various body compartments examined was found when normal lymphocytes were injected into either type of recipient. However, when pertussis lymphocytes were injected into normal mice there was no interrelationship between the changes in the node with those in the blood, liver, lung, or spleen. In the case of pertussis lymphocytes transfused into pertussis-treated mice no interrelationship between any two compartments was observed. It was concluded that in pertussis-treated mice there is an inhibition of lymphocyte emigration which is primarily the consequence of an effect on the cell.

Animals↗

Leukocytosis and resistance to septic shock in intercellular adhesion molecule 1-deficient mice.

Intercellular adhesion molecule 1 (ICAM-1) is one of three immunoglobulin superfamily members that bind to the integrins lymphocyte function associated 1 (LFA-1) and Mac-1 on leukocytes. We have generated mice that are genetically and functionally deficient in ICAM-1. These mice have elevated numbers of circulating neutrophils and lymphocytes, as well as diminished allogeneic T cell responses and delayed type hypersensitivity. Mutant mice are resistant to lethal effects of high doses of endotoxin (lipopolysaccharide [LPS]), and this correlates with a significant decrease in neutrophil infiltration in the liver. Production of inflammatory cytokines such as tumor necrosis factor alpha or interleukin 1 is normal in ICAM-1-deficient mice, and thus protection appears to be related to a diminution in critical leukocyte-endothelial interactions. After sensitization with D-galactosamine (D-Gal), ICAM-1-deficient mice are resistant to the lethal effect of low doses of exotoxin (Staphylococcus aureus enterotoxin B [SEB]), which has been shown to mediate its toxic effects via the activation of specific T cells. In this model, ICAM-1-mediated protection against SEB lethality correlates with a decrease in the systemic release of inflammatory cytokines, as well as with prevention of extensive hepatocyte necrosis and hemorrhage. ICAM-1-deficient mice sensitized with D-Gal, however, are not protected from lethality when challenged with low doses of endotoxin (LPS). These studies show that the different contribution of ICAM-1 in the activation of either T cells or macrophages is decisive for the fatal outcome of the shock in these two models. This work suggests that anti-ICAM-1 therapy may be beneficial in both gram-positive and -negative septic shock, either by reducing T cell activation or by diminishing neutrophil infiltration.

Animals↗

Persistent urethral leukocytosis and asymptomatic chlamydial urethritis.

Chlamydia trachomatis was isolated from 47% of asymptomatic, sexually active men whose urethral smears contained four or more polymorphonuclear leukocytes (PMN) per high-power field (hpf) one week after their sexual activity was restricted. C. trachomatis was not detected in any of 23 asymptomatic, sexually active men having less than 4 PMN/hpf in two urethral smears obtained one week apart. Semiquantitation of urethral PMN in the urethral Gram-stained smear is useful in the evaluation of asymptomatic men without gonorrhea who are concerned about the possibility of harboring a urethral pathogen.

Chlamydia Infections↗

Bacteremia in febrile children with lobar pneumonia and leukocytosis.

A retrospective analysis of 86 consecutive cases of childhood pneumonia with clinical features indicative of bacterial etiology was performed to delineate the prevalence of and characteristics associated with accompanying bacteremia. All patients had temperature greater than or equal to 40 degrees C, a lobar pulmonary infiltrate on chest radiograph, and a peripheral white blood cell concentration greater than 20,000/mm3 or absolute band count greater than 2,000/mm3. Associated clinical findings included 44% with an "ill" appearance, 37% with respiratory rate greater than or equal to 60/minute, 20% with heart rate greater than or equal to 200/minute, 33% with otitis media. Only one of 86 patients had a bacterial pathogen isolated by blood culture (Haemophilus influenzae, type b). In children older than four months of age with pneumonia whose characteristics are indicative of bacterial etiology, associated clinical findings and laboratory data are insensitive markers for distinguishing those with concomitant bacteremia. The rate of bacteremia in this group of patients is low; if the clinical situation warrants, most with these features do not require empiric hospitalization with parenterally administered antibiotic therapy pending blood culture results.

Adolescent↗

Didemnin B--an immunosuppressive cyclic peptide that stimulates murine hemagglutinating antibody responses and induces leukocytosis in vivo.

Didemnin B (DB) is a cyclic peptide with potent immunosuppressive activity in vitro and in the murine graft-versus-host-reaction (GVHR), the only measure of in vivo immunity tested in our prior studies. Because continued production of mature leukocytes by bone marrow and an intact antibody response are crucial to defense against infection in immunosuppressed patients, we have evaluated the effects of DB on these processes as well. Anti-sheep red blood cell (SRBC) hemagglutinating antibody (hAb) production was induced by i.p. injection of 5 x 10(7) SRBC in CB6F1 mice (5/group) treated with vehicle or DB once/day for six days. Serum was collected on day 7 and hAb titers measured by SRBC agglutination. Control antibody titers were 1/16, while animals receiving DB doses of 0.025, 0.05, 0.10, and 0.20 mg/kg/day yielded titers of 1/37, 1/74, 1/56, and 1/74, respectively. This stimulation of hAb production (4.6 x control) was confirmed by a second experiment. We then studied DB effects (0.1 mg/kg/day x 6 days) on serum hAb titers in separate groups of five mice at 7, 10, 15, and 20 days postimmunization. Control hAb titers were 1/110 on day 7, then dropped to 1/60 on days 10, 15, and 20. DB-treated animals had titers of 1/130 on day 7, and 1/170 on days 10-20. These data show that DB treatment in vivo causes a persisting increase in anti-SRBC hAb titers. Evaluation of DB effects on proliferation and antibody secretion in vitro by three hybridoma cell lines showed a potent inhibition of cell replication but stimulation of antibody production on a per-cell basis in each clone (+26%-+900%, range), suggesting a direct effect on Ig synthesis. During our first in vivo DB studies (0.1 mg/kg/day x 7 days) in mice, we noted that peripheral blood white counts were elevated on day 8 to 21.3 +/- 2.1 x 10(3)/mm3 compared with control (vehicle only) levels of 13.6 +/- 2.0 x 10(3)/mm3 (P less than .01). Kinetic studies showed that by 24 hr after a single i.p. injection of DB (1.0 mg/kg), blood leukocyte, granulocyte, and lymphocyte counts were elevated by 2.5-, 3-, and 2-fold, respectively, but declined rapidly thereafter. 3H-thymidine incorporation (4 hr) by freshly harvested bone marrow leukocytes from DB-treated mice (0.025, 0.05, and 0.10 mg/kg/day x 7 days) was enhanced up to 40% over control (P less than .05), while bone marrow cellularity was increased 200% (P less than .01).(ABSTRACT TRUNCATED AT 400 WORDS)

Animals↗