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Biomedical subjects

L B Lachman

Publications and source records attributed to L B Lachman.

At least 55 records · Page 3Linked to original sources
PubMed1986

Fish lymphocytes respond to human IL-1.

IL-1 is known to cross species barriers in that IL-1 of one mammalian species can interact with cells of other mammalian species. The work described herein demonstrates that IL-1 can cross phylogenetic classes as IL-1 derived from human peripheral blood lymphocytes (PBL) potentiated the proliferative response of catfish lymphocytes to the T cell mitogen Concanavalin A (ConA). Catfish PBL were separated by density gradient centrifugation and used in blastogenic transformation assays. IL-1 had relatively little direct stimulatory effect but with suboptimal amounts of ConA there was a significant augmentation of the proliferative response. The specificity of the response was determined by neutralization experiments in which anti-human IL-1 antibody significantly diminished the reaction of catfish lymphocytes to IL-1.

Animals↗
PubMed1985

Interleukin-1 stimulation of astroglial proliferation after brain injury.

The interleukins, which have a regulatory role in immune function, may also mediate inflammation associated with injury to the brain. In experiments to determine the effect of these peptide hormones on glial cell proliferation in culture, interleukin-1 was a potent mitogen for astroglia but had no effect on oligodendroglia. Interleukin-2 did not alter the growth of either type of glial cell. Activity similar to that of interleukin-1 was detected in brains of adult rats 10 days after the brains had been injured. These findings suggest that interleukin-1, released by inflammatory cells, may promote the formation of scars by astroglia in the damaged mammalian brain.

Animals↗
PubMed1985

Human B-lymphocyte colony responses: suboptimal colony responsiveness in aged humans associated with defective function of B cells and monocytes.

The abilities of human B cells from young and aged subjects to form colonies in semisolid cultures stimulated with Staphylococcus protein A were investigated. Approximately three-fourths of aged adults had significantly diminished colony responses compared to young adults. In 55% of these aged adults, the in vitro blocking of monocyte prostaglandin synthesis lead to a 1.5-fold or greater augmentation of the depressed colony responses. Other experiments showed that the improvement with indomethacin could not be explained by the greater sensitivity of aged versus young B-cell colony precursors to prostaglandin suppression. However, indomethacin failed to improve the depressed colony responses of the remaining aged adults. This failure could not be attributed to deficient interleukin 1 production, detectable alterations in accessory cell subsets of monocytes, or the lack of potential colony precursors bearing sIgD/M. Instead, the B cells from these aged subjects demonstrated a substantial decrease in the capping of sIgD/M compared to the B cells of aged subjects which displayed improved colony responses with indomethacin and compared to the B cells from young adults. Thus, these data indicate that the diminished B-cell colony responses of aged humans represent aberrancies within both the B-cell and monocyte lineages which might coexist.

Adult↗
PubMed1985

Sodium periodate-induced T cell mitogenesis: an analysis of the requirement for Ia and IL 1.

T lymphocytes oxidized with the mitogen sodium periodate undergo a proliferative response when cultured in the presence of Ia+ accessory cells. However, the exact role(s) the accessory cells play in such a response has not been clearly defined. We have evaluated the role of Ia and the requirement for interleukin 1 (IL 1) in periodate mitogenicity by using the Ia+ cloned tumor cell lines P388AD (Ia+, IL 1 inducible) and P388NA (Ia+, IL 1 noninducible) as accessory cells. P388AD but not P388NA was able to supply accessory cell function to periodate-treated T cells, suggesting that Ia expression alone was not sufficient to reconstitute a response. Monoclonal anti-I-Ad and anti-I-Ed antibody blocked the accessory cell function of P388AD. In addition, monoclonal antibody GK 1.5, directed against the T cell determinant L3T4a, blocked the P388AD/periodate-treated T cell interaction, confirming that this interaction was restricted by class II molecules. Although Ia expression was required, the response was not major histocompatibility complex (MHC) restricted, because allogeneic as well as syngeneic macrophages were capable of supplying accessory cell function to periodate-treated T cells. Exogenous IL 1 alone was able to trigger periodate-treated T cells, suggesting that Ia was required for the induction of IL 1 synthesis by the accessory cells. Furthermore, purified IL 2, devoid of IL 1 activity, was able to fully reconstitute the proliferative response of accessory cell-depleted oxidized T cells to a level equal to that of whole spleen accessory cells or P388AD. These data suggest that periodate-treated T cells can proliferate with IL 1 alone and that Ia+ accessory cells in periodate-mediated T cell mitogenicity may function in the release of IL 1 and the induction of IL 2 synthesis by the T cells.

Animals↗
PubMed1985

Differential abilities of human peripheral blood monocytes quantitatively or qualitatively differing in HLA-DR and HLA-DS expression to support B cell activation in liquid and semisolid cultures.

The present investigation was performed to determine whether the activation of human B cells by Staphylococcal protein A (SpA) in liquid and semi-solid cultures might be dependent on distinct subsets of peripheral blood mononuclear-phagocytes (M phi) defined by the expression of HLA-DR and HLA-DS determinants. Highly pure HLA-DR- M phi functioned as effectively as HLA-DR+ MO in supporting B cell liquid proliferative responses when SpA was continuously present in cultures. However, HLA-DR+ M phi were two to three times more effective than HLA-DR- M phi in promoting B cell proliferative responses when either M phi or B cells were pulsed with SpA and were then cultured without supplemental SpA. Similarly, B cell activation in semisolid cultures was crucially dependent on HLA-DR+ M phi because colony responses were reduced fivefold in the presence of M phi expressing low/intermediate HLA-DR levels compared to M phi-containing cells with high HLA-DR levels. HLA-DS- M phi isolated by two different techniques were more effective than HLA-DS+ M phi in supporting both liquid proliferative and colony responses of B cells. Flow microcytofluorometry analysis of the dual expression of HLA-DR and HLA-DS on highly pure HLA-DR- M phi and HLA-DR+ M phi revealed that both HLA-DR- and HLA-DR+ M phi expressed low levels of HLA-DS. Importantly, the expression of HLA-DS on HLA-DR- M phi was bimodal, with an HLA-DR-, DS+ subset and an HLA-DR-, DS-subset being present. Other experiments supported the conclusions that the differential abilities of the HLA-DR-, -DS-defined subsets of M phi to support B cell activation did not represent M phi suppressive effects or differences in IL 1 production. Collectively, these results indicate that B cell activation can be directly supported by M phi whose predominant phenotype is HLA-DR+, -DS-. Thus, the accessory cell pathway of B cell activation described here is distinct from the pathway known to be required for T cell responsiveness, and could serve to provide early alternative or ancillary signals for triggering B cells.

Adult↗
PubMed1984

Induction of fibroblast proliferation by interleukin-1 derived from human monocytic leukemia cells.

Human interleukin-1 (IL-1), free of contaminating lymphokines, was isolated from cultures of purified monoblasts from a patient with acute monocytic leukemia. Partially purified IL-1 (diafiltration, ultrafiltration, and isoelectric focusing) stimulated proliferation of subconfluent human fibroblasts in vitro. Further purification of IL-1 by high-resolution gel filtration- and anion exchange-high performance liquid chromatography revealed that fibroblast proliferation activity could not be separated from IL-1 activity (thymocyte proliferation), suggesting that both activities are the properties of a single molecule. Fibroblasts and thymocytes exhibited a similar sensitivity to the proliferative effects of IL-1. These findings suggest that macrophages participating in inflammatory reactions in vivo might release IL-1, which could function to expand fibroblast populations at sites of inflammatory reactions, by acting as a fibroblast growth factor.

Cell Division↗
PubMed1984

Lipopolysaccharide (LPS) modulation of human monocyte accessory cell function in promoting T-cell colonies: inability of LPS and IL-1 to abrogate the need for monocytes with high HLA-DR expression.

The abilities of human monocytes differentially expressing HLA-DR and of lipopolysaccharide (LPS) to influence T-cell colony responses were investigated. Optimal T-cell colony responses stimulated by soluble Staph protein A were crucially dependent on monocytes. Also, monocyte facilitation of colony responses was markedly inhibited by 10 micrograms/ml LPS and the addition of indomethacin reversed this inhibition. In contrast the inhibition of T-cell colony responses with 100 micrograms/ml LPS was not reversed with indomethacin and preincubation experiments with high concentrations of LPS showed the inhibition could be mediated through T cells by mechanisms other than prostaglandins. The treatment of monocytes with a monoclonal anti-HLA-DR reagent + C reduced the frequencies of monocytes expressing high levels of HLA-DR approximately fivefold and the resulting monocytes which expressed low levels of HLA-DR also poorly functioned in the promotion of colony responses compared to controls. LPS in the presence of indomethacin improved the ability of monocytes expressing low levels of HLA-DR to promote colony responses. However, these monocytes consistently failed to augment colony responses to those levels observed with untreated monocytes and their failure was not secondary to deficient interleukin 1 release. These results indicate that although LPS can somewhat potentiate the accessory cell function of certain human monocytes, it cannot abrogate an additional requirement for those monocytes expressing high levels of HLA-DR.

Adult↗
PubMed1984

Growth of a cloned helper T cell line induced by a monoclonal antibody specific for the antigen receptor: interleukin 1 is required for the expression of receptors for interleukin 2.

By using as an experimental system the induction of growth of a cloned, antigen:Ia-reactive helper T cell line by an antigen receptor-specific monoclonal antibody, we demonstrated that growth requires two essential co-factors, exogenously produced IL 1 and endogenously produced IL 2. The primary role of the IL 1 is in the expression of receptors on the T cell surface for IL 2, rather than for promoting the synthesis of IL 2. The use of a clone-specific activating monoclonal antibody at nanogram amounts to activate a cloned helper T cell should allow a detailed characterization of T cell activation via antigen receptor cross-linking.

Animals↗
PubMed1983

Lymphokine-activated killer cell phenomenon. III. Evidence that IL-2 is sufficient for direct activation of peripheral blood lymphocytes into lymphokine-activated killer cells.

Purified interleukin 2 (IL-2) was found to be sufficient for direct activation of peripheral blood lymphocytes into lymphokine-activated killer (LAK) cells. The LAK activation factor was directly and consistently associated with IL-2 activity using classic protein purification techniques, adsorption to IL-2-dependent cell lines, and inhibition with anti-Tac antibody. As yet, no other cytokines have been found that perform the same role.

Antibodies, Monoclonal↗
PubMed1983

Interleukin 1 stimulation of collagenase production by cultured fibroblasts.

Interleukin 1 is a monokine that exerts biological effects on a variety of target cells in vitro. In this report, interleukin 1 has been found to be capable of stimulating collagenase production by cultured dermal fibroblasts. The concentrations of interleukin 1 that stimulate fibroblast collagenase production are similar to those that stimulate mouse thymocyte proliferation. Analyses by high performance liquid chromatography indicate that interleukin 1, rather than a contaminating monokine, is responsible for this effect on fibroblasts. Interleukin 1, released in vivo by macrophages infiltrating sites of tissue damage or inflammation, may function to stimulate the release of collagenase by connective tissue fibroblasts.

Chromatography, High Pressure Liquid↗
PubMed1983

Human interleukin 1: purification and properties.

Human interleukin 1 (IL 1) has been purified to homogeneity by a procedure of molecular weight fractionation, isoelectric focusing, and preparative polyacrylamide gel electrophoresis. The homogeneity of the purified material has been demonstrated by silver staining of analytical polyacrylamide gels. The homogeneous IL 1 retains only a trace of its original biological activity because of the denturing effects of the sodium dodecyl sulfate used in the final step of purification. Very highly purified IL 1, retaining strong biological activity, has been eluted from nondenaturing polyacrylamide gels. This IL 1 has been demonstrated to stimulate human and mouse T and B lymphocytes, fibroblasts, and synovial cells. In addition, in vivo treatment of animals with IL 1 resulted in the immunologically relevant symptoms of fever, increased plasma levels of acute phase proteins, and increased numbers of circulating neutrophils.

Animals↗
PubMed1982

Streptococcal cell walls and synovial cell activation. Stimulation of synovial fibroblast plasminogen activator activity by monocytes treated with group A streptococcal cell wall sonicates and muramyl dipeptide.

Group A streptococcal peptidoglycan has previously been shown to be arthritogenic in rats and has been implicated as a structure present in a class of possible etiologic agents for rheumatoid arthritis. The present study reports that conditioned medium from human monocytes, after interaction with cell wall sonicates of four group A streptococcal strains, stimulates the plasminogen activator (PA) activity of nonrheumatoid synovial fibroblasts. Low concentrations of N-acetylmuramyl-L-alanyl-D isoglutamine (muramyl dipeptide) can also generate this synovial activator (SA) activity from human monocytes. Preliminary biochemical data suggest that the SA activity is distinct from interferon-gamma, interleukin 1, and interleukin 2. These results indicate that agents that are arthritogenic in rats can modulate human synovial fibroblast functions via monocytes. The findings are proposed to have possible significance for an understanding of the cellular interactions involved in the formation and function of the rheumatoid pannus, because PA has been invoked as possibly being generally important for the processes of cell migration, tissue remodeling, and inflammation.

Acetylmuramyl-Alanyl-Isoglutamine↗