Biomedical subjects

G L Howells

Publications and source records attributed to G L Howells.

23 records · Page 2Linked to original sources

PubMed1993

Peripheral blood lymphocytes express the platelet-type thrombin receptor.

Northern blot analysis of human mononuclear cells indicated that the platelet thrombin receptor may be expressed by lymphocytes. In order to investigate this, we prepared affinity purified rabbit antibodies against the thrombin receptor which bound platelets and blocked thrombin activation. Using flow cytometry on peripheral blood cells, we found that the vast majority of NK cells (CD16/CD56 positive) and a fraction of CD3/CD4 positive T cells expressed the thrombin receptor. B cells, neutrophils and monocytes were negative. These data suggest that potentially thrombin may play a direct role in regulating NK and T cell function.

Antibodies↗

PubMed1991

Platelet-derived interleukin 1 induces human endothelial adhesion molecule expression and cytokine production.

Interleukin 1 (IL-1) plays a central role in the regulation of the body's response to infectious and inflammatory stimuli. Recent evidence has shown that human platelets express a cell associated form of this proinflammatory cytokine very rapidly following activation. Since one of the earliest events in inflammation is frequently the rapid adhesion of platelets to injured endothelium, it was of interest to determine whether platelets express IL-1 in a functionally relevant form that can alter the phenotype of human endothelial cells in vitro. Thrombin activated platelets induced significant expression of the adhesion molecule intercellular adhesion molecule 1, as well as secretion of the IL-1 inducible cytokines IL-6 and granulocyte macrophage colony stimulating factor by cultured human umbilical cord and saphenous vein endothelial cells. This was inhibited by prior treatment of the platelets with antibody specific for IL-1. These results suggest that platelet delivered IL-1 might initiate and regulate some of the earliest phases of the inflammatory response. An additional observation of interest was differential induction of endothelial leucocyte adhesion molecule 1 by activated platelets on saphenous vein but not umbilical vein but not umbilical vein endothelial cells, which suggests functional heterogeneity of the endothelial cells.

Adult↗

PubMed1988

Antibodies against monocytes and endothelial cells in the sera of patients with atherosclerotic peripheral arterial disease.

We looked for antibodies against endothelial cells, monocytes, fibroblasts, lymphocytes and Epstein-Barr virus transformed lymphocytes in the sera of 28 elderly and 18 middle-aged patients with atherosclerotic peripheral arterial disease and 13 controls. Inclusion criteria were symptomatic peripheral arterial disease with intermittent claudication and ankle/radial Doppler pressure ratio less than 0.7 in the patient group and greater than 1 in the controls. The sera were tested using a standard cytotoxic technique against a cell panel of monocytes, T and B lymphocytes from 5 donors, and against endothelial cells, fibroblasts and Epstein-Barr virus transformed lymphocytes from one umbilical cord vein and blood. The sera of 30 of 46 (65.2%) patients showed toxicity against monocytes from at least one member of the cell panel and 12 of 19 sera tested (63%) reacted with endothelial cells. Only one of the control sera was positive against monocytes and none reacted with endothelial cells. None of the sera of either patients or controls contained cytotoxic antibodies against T and B lymphocytes, Epstein-Barr virus transformed lymphocytes or fibroblasts. The selective cytotoxicity suggests that the antibodies detected are not against HLA-antigens (which are expressed by normal lymphocytes and Epstein-Barr virus lymphocytes). Our results suggest that immune phenomena occur in atherosclerosis.

Aged↗

PubMed1988

Interleukin 1 (IL-1) and tumour necrosis factor synergise in the induction of IL-1 synthesis by human vascular endothelial cells.

We have demonstrated that recombinant interleukin 1 (IL-1) induces IL-1 alpha and IL-1 beta production by human vascular endothelial cells (EC) in vitro. The effect of IL-1 on EC was dose-dependent and not due to contamination by endotoxin or secondary to the production of tumour necrosis factor (TNF). Thymocyte co-mitogenesis was shown to be due to IL-1 by treating EC supernatants with neutralising antibodies specific for IL-1 alpha and IL-1 beta. Recombinant TNF alpha synergised with IL-1 in the induction of IL-1 secretion by EC. Synergy was particularly striking at concentrations of IL-1 and TNF which, when used alone, had no effect - 2 U/ml IL-1 with 10 U/ml TNF. Thus we provide more evidence that EC play an important role in the perpetuation or possibly even initiation of chronic inflammation by amplifying cytokine production initiated by small numbers of infiltrating leucocytes.

Dose-Response Relationship, Drug↗

PubMed1987

The sequential demonstration of non-specific esterase reactivity Ia antigen and Thy-1 antigen in murine epidermal sheets.

Immunofluorescence demonstrating Ia and Thy-1 antigens and non-specific esterase (NSE) enzyme histochemistry were performed sequentially on sheets of ear epidermis from CBA, C3H.OH, A/J, and Balb/c mice. The same areas of epidermis were photographed after each reaction and individual cells identified and compared. Thy-1+ dendritic cells expressed neither Ia antigen nor NSE reactivity. No cell was found to express Ia antigen or NSE alone: thus all Langerhans cells (LC) in normal murine epidermis appeared to co-express Ia antigen and NSE reactivity. LC expressing greatly increased amounts of Ia antigen were occasionally seen apposed to Thy-1+ cells suggesting that these cells may be immunologically active--perhaps involved in antigen presentation.

Animals↗