Cyclosporine suppression of lymphocyte recruitment, regional blood flow, and vascular permeability at sites of allogeneic cellular interactions

Journal Article · Mon Aug 01 04:00:00 EDT 1983 · Surgery; (United States)

OSTI ID:5545838

Hanto, D W; Harty, J T; Hoffman, R; Simmons, R L

Although cyclosporine (CsA) has been thought to act primarily on the afferent phase of the immune response, we can demonstrate that it also acts at the efferent phase. The effect of CsA on lymphocyte recruitment (LR), regional blood flow (RBF), and vascular permeability (VP) was studied in paired, healed, subcutaneously placed urethane sponge grafts inoculated with specifically sensitized lymphocytes (SSLs) and allogeneic target cells. Intravenous injection of /sup 111/In-labelled unsensitized lymphocytes, /sup 86/RbCl and /sup 125/I-labelled albumin were used to assess LR, RBF, and VP, respectively. Suspensions of SSL and targets in CsA at 10 and 1 microgram/ml prior to graft inoculation markedly reduce the preferential increase in LR to the site of interaction between SSLs and targets bearing the sensitizing alloantigen (P less than 0.002 for both). Similarly, CsA blocks the preferential increase in RBF (P . 0.017) and VP (P less than 0.002) to the graft site. These effects persist for at least 24 hours. If SSLs and targets are washed after incubation with CsA, LR is still reduced. These results are consistent with the idea that cell-bound CsA blocks the elaboration of lymphokines which results from the interaction between SSLs and specific alloantigen in vivo. These lymphokines increase RBF and VP and are accompanied by an increase in LR. Inhibition of these vascular effects may prevent the recruitment of additional lymphocytes to the graft site. CsA may, therefore, prevent or interrupt allograft rejection by blocking amplification of the rejection mechanism at the graft site.

• Research Organization: Department of Surgery, University of Minnesota Health Sciences Center, Minneapolis
• OSTI ID: 5545838
• Journal Information: Surgery; (United States), Journal Name: Surgery; (United States) Vol. 94:2; ISSN SURGA
• Country of Publication: United States
• Language: English

Related Subjects

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59 BASIC BIOLOGICAL SCIENCES
ALBUMINS
ALKALI METAL ISOTOPES
ANIMAL CELLS
BETA DECAY RADIOISOTOPES
BETA-MINUS DECAY RADIOISOTOPES
BIOLOGICAL EFFECTS
BIOLOGICAL MATERIALS
BLOOD
BLOOD CELLS
BLOOD FLOW
BODY FLUIDS
CONNECTIVE TISSUE CELLS
DAYS LIVING RADIOISOTOPES
DRUGS
ELECTRON CAPTURE RADIOISOTOPES
ENZYME ACTIVITY
GRAFT-HOST REACTION
IMMUNE REACTIONS
INDIUM 111
INDIUM ISOTOPES
INHIBITION
INTERMEDIATE MASS NUCLEI
IODINE 125
IODINE ISOTOPES
ISOMERIC TRANSITION ISOTOPES
ISOTOPE APPLICATIONS
ISOTOPES
LABELLING
LEUKOCYTES
LYMPHOCYTES
LYMPHOKINES
MATERIALS
MINUTES LIVING RADIOISOTOPES
NUCLEI
ODD-EVEN NUCLEI
ODD-ODD NUCLEI
ORGANIC COMPOUNDS
PROTEINS
RADIOISOTOPES
RUBIDIUM 86
RUBIDIUM ISOTOPES
SOMATIC CELLS
TRACER TECHNIQUES