Complement-dependent lymphocytotoxic antibodies (CLA) in systemic lupus erythematosus preferentially inhibit the generation of alloreactive cytotoxic T cells in secondary CML.

Complement-dependent lymphocytotoxic autoantibodies (CLA) are invariably present in sera of patients with active systemic lupus erythematosus (SLE). This study aimed to test for the influence of such antibodies on the in vitro generation of human alloantigen reactive proliferative and cytotoxic T cell responses. Unsensitized or alloantigen primed memory cells were pre-treated with CLA in the presence or absence of complement. Following stimulation of the remaining cells with allogeneic peripheral blood mononuclears, the proliferative and cytotoxic capacity was evaluated. Results indicated that only pre-treatment with CLA and complement influenced these reactions whereas in the absence of complement antibodies were totally ineffective. Pre-treatment of unsensitized precursor cells reduced and delayed both proliferative and cytotoxic reactivity; in contrast, pre-treatment of memory cells exclusively reduced cellular cytotoxicity. It thus appears that such SLE associated autoantibodies in the presence of complement are capable of modifying the balance between different subsets of alloreactive T cells.     

Metabolic and Functional Characteristics of Alveolar Macrophages Recovered from Rats Exposed to Marijuana Smoke

Pulmonary alveolar macrophages were obtained by bronchopulmonary lavage from male rats after 30 consecutive days of in vivo exposure to marijuana and tobacco smoke. No significant differences were found between either group of experimental animals and controls in the number of cells recovered, the protein content per 10(6) cells, or the percentage of cells that adhered to plastic surfaces. The ability of macrophages to phagocytize viable bacteria was not affected by exposure to either marijuana or tobacco smoke in that both treatment groups ingested Staphylococcus aureus over a 60-min period as well as did control cells. Differences were found between the groups, however, with respect to cellular metabolism. Marijuana smoke inhalation caused a small decrease in the amount of oxygen consumed by macrophages during phagocytosis, as compared with control cells. This may have been reflected in the even greater decrease in superoxide formation observed during particle engulfment by these treated cells. Tobacco smoke, on the other hand, increased oxygen consumption and was without effect on superoxide release. Neither tobacco nor marijuana smoke treatment had an effect on the direct oxidation of glucose via the hexose monophosphate shunt. Our results indicate that, despite several metabolic alterations in response to marijuana and tobacco smoke, alveolar macrophages were not compromised with respect to their ability to ingest a particulate challenge.     

Allelic and nonallelic heterogeneity in dyschondrosteosis (Leri-Weill syndrome)

Dyschondrosteosis (DCS) is an autosomal dominant form of mesomelic dysplasia that has been recently ascribed to large-scale deletions and nonsense mutations of the SHOX gene on the pseudoautosomal region of chromosome X and Y [Belin et al., 1998: Nat Genet 19:67-69; Shears et al., 1998: Nat Genet 19:70-73]. Here, we report the molecular analysis of a total of 23 DCS families including 16 previously reported pedigrees [Belin et al., 1998: Nat Genet 19:67-69; Huber et al., 2001: J Med Genet 38:281-284] and 7 novel DCS families. Linkage analyses in 21 of 23 families were consistent with linkage to the pseudoautosomal region. However, in 2 of 23 families, linkage studies excluded SHOX as the disease-causing gene, suggesting that this condition is genetically heterogeneous.     

Beta2 integrins control the severity of murine Lyme carditis

Infection of C57BL/6 (B6) mice with the Lyme disease spirochete Borrelia burgdorferi can result in development of arthritis and carditis. B. burgdorferi induces expression of beta2/CD18 integrins, adhesion molecules that mediate the firm adhesion of leukocytes to the endothelium necessary for cellular extravasation during inflammation. The important role of beta2/CD18 integrins during extravasation suggests that these molecules play a role in the development of Lyme arthritis and carditis. The dependency of these inflammatory processes on the beta2 integrins was investigated in CD18 hypomorph mice, which express low levels of CD18. The results indicate that CD18 deficiency did not abrogate development of Lyme arthritis or carditis. Moreover, it resulted in increased severity of Lyme carditis. B. burgdorferi-infected CD18 hypomorph mice showed an increased macrophage infiltration of the heart, while they produced lower levels of borreliacidal anti-B. burgdorferi antibodies compared to wild-type mice. In accordance with these results, we demonstrate that dendritic cells from CD18 hypomorph mice secrete higher levels of monocyte/macrophage chemoattractant protein 1 (MCP-1/CCL2) in response to B. burgdorferi. Similarly, we show by real-time PCR that B. burgdorferi-infected hearts from CD18 hypomorph mice express increased levels of MCP-1 RNA compared to wild-type mice. Overall, our results indicate that beta2 integrin deficiency does not abrogate B. burgdorferi-induced inflammation; rather, it results in increased recruitment of macrophages into the B. burgdorferi-infected heart, likely due to the increased expression of MCP-1 in this tissue. Thus, beta2 integrins may play a regulatory role in B. burgdorferi-induced inflammation beyond mediating adhesion of leukocytes to the endothelium.     

Weight loss in patients with hematological neoplasias is associated with immune system stimulation

Summary Weight loss is the main symptom of so-called tumor cachexia. The pathogenetic mechanisms underlying cachexia are poorly understood; however, it appears that enhanced formation of cytokines such as interferon- and tumor necrosis factor- are involved. In 94 patients suffering from hematological neoplasias we compared body weight changes with serum neopterin, tryptophan, and kynurenine. Biochemical changes, the formation of neopterin, the degradation of tryptophan are closely related to interferon- activity. The majority of our patients had increased neopterin and decreased tryptophan concentrations. Weight loss was seen particularly in patients with higher neopterin and lower tryptophan values. An association between higher neopterin levels and greater weight loss was apparent at study entry and during the follow-up of patients. Our data support the concept that weight loss is closely linked to endogenous interferon- activity.Abbreviations NHL non-Hodgkin's lymphoma - HD Hodgkin's disease - MM multiple myeloma - MGUS monoclonal gammopathy of unknown significance - IFN- interferon- - TNF- tumor necrosis factor-