Disease relevance of CD18

• OBJECTIVE: The expression of the leukocyte CD18 adhesion complex on polymorphonuclear leukocytes (PMNs) was measured, and the physiologic effects of blockade of the complex were studied after trauma and sepsis [1].
• Where indicated, CD18 antibody IB4 was infused systemically at 30 min of ischemia [2].
• Retroinfusion of NFkappaB decoy oligonucleotide extends cardioprotection achieved by CD18 inhibition in a preclinical study of myocardial ischemia and retroinfusion in pigs [2].
• 3. These data suggest that, in this model of septic ALI, neutropenia is, in part, CD18 dependent and that blocking CD18-dependent PMN adhesion protects the alveolar-capillary membrane independently of altered hemodynamic status [3].
• Transient inhibition of CD18-dependent leukocyte functions after hemorrhage and polymicrobial sepsis [4].

High impact information on CD18

• Blockade of CD18 showed this adhesion molecule to be critical for eosinophil accumulation, and LPS-primed sites were inhibited as effectively as nonprimed sites [5].
• The CD18 receptors were blocked with monoclonal antibodies either immediately before trauma or immediately before an endotoxin (lipopolysaccharide [LPS]) challenge that was administered to all groups 3 days after the shock episode [1].
• We conclude that NFkappaB decoy ODN transfection by retroinfusion is feasible in pig hearts and provides postischemic cardioprotection in addition to CD18 blockade [2].
• Additional systemic application of CD18-antibody IB4 (1.5 mg/kg) did not alter infarct size or SES in comparison to GSH/cariporide retroinfusion alone [6].
• Pretreatment with anti-CD11/CD18 monoclonal antibody and superoxide dismutase-polyethylene glycol significantly reduced neutrophil infiltration and normalized transepithelial electrical resistance and mannitol fluxes [7].

Chemical compound and disease context of CD18

• METHODS: Pigs were pretreated with anti-CD11/CD18 monoclonal antibody, superoxide dismutase-polyethylene glycol, or saline solution before inducing 1 hour of ischemia [7].

Biological context of CD18

• CD18 up-regulation increased similarly in the two groups during CPB.(ABSTRACT TRUNCATED AT 250 WORDS)[8]
• RESULTS: The infusion of endotoxin was followed by granulocytopenia, reduced oxidative burst activity, increased expression of CD18 and decreased expression of CD62L on granulocytes [9].
• Following endotoxin we observed a pronounced lymphocytopenia and an increased secretion of IL-8 and IL-10, a decrease in the expression of CD18 on lymphocytes and in the stimulated lymphocyte proliferation and in the chemotaxis of granulocytes [10].
• Epitope mapping studies by competitive binding of mAb by flow cytometric analysis based on PNK-I as CD18 epitope defining antibody resulted H20A and MHM23 mAbs bind to the same shared epitope as PNK-I, but MUC76A and MUC93A mAbs were distinct from PNK-I [11].
• Inhibition of CD18-dependent adherence of polymorphonuclear leukocytes does not affect liver oxygen consumption in fecal peritonitis in pigs [12].

Anatomical context of CD18

• The results suggest that the CD18 integrin is involved in the recruitment of leukocytes to the airways, but increased numbers of eosinophils in lavage fluid are not an essential correlate of bronchial hyperresponsiveness in this model [13].
• Here we demonstrate the involvement of ICAM-1-, CD18- and RGD-dependent adhesion mechanisms in chondrocyte-T-cell adhesion and in cell-mediated killing of chondrocytes in vitro [14].
• The adhesion molecules CD18 and CD62 on lymphocytes were measured using monoclonal antibodies, and the lymphocyte proliferation was measured without stimulation and in response to mitogens [10].
• Significant numbers of the histiocytes were positive for the integrins CD18 and VLA-4 (CD49d), indicating involvement of integrin pathways in the spread or growth, or both, of the leiomyofibrosarcoma [15].

Associations of CD18 with chemical compounds

• Survival of guinea pig cardiac xenografts in C6-deficient PVG rats treated with monoclonal antibody to CD18 [16].
• In this study we compared alveolar (ALV), systemic arterial (SA), and pulmonary arterial (PA) PMNs CD18 receptor expression, measured by fluorescent immunophenotyping and, O2- generation, measured by reduction of ferricytochrome C, in septic swine [17].
• Platelet activating factor (PAF) stimulates PMNs by CD18-independent pathways, and WEB-2086, a PAF receptor antagonist, blunts septic symptoms in many experimental models [18].
• Plasma tumor necrosis factor activity, blood polymorphonuclear leukocyte counts, and CD18 expression were unaffected by the administration of pentoxifylline [19].
• Thus, cardiac dysfunction occurs after activation of the complement cascade with zymosan resulting in extraction of granulocytes mediated by the CD18 adherence glycoprotein [20].

Other interactions of CD18

• Flow cytometric measurements of CD18 and CD45 expression were performed [21].
• Systemic neutrophil surface receptor (CD18) expression was analyzed with monoclonal antibodies, and flap skin biopsy specimens were analyzed for neutrophil infiltration [22].
• In the absence of cytokine stimulation, chondrocyte-peripheral blood mononuclear cell (PBMC) interactions were unaffected by inhibition of ICAM-1-dependent pathways but were significantly reduced by blockade of CD18- and RGD-dependent pathways [14].
• Two minutes after protamine administration, CD18 (beta-subunit of Mac-1) expression measured by immunofluorescence flow cytometry increased 128 +/- 9% (mean +/- SEM) over preprotamine levels in control piglets but remained unchanged in NPC piglets (99 +/- 2%, P < 0.05) [23].

Analytical, diagnostic and therapeutic context of CD18

• The CD18 density on circulating PMNs was determined with flow cytometry using mean channel fluorescence (MCF) [1].
• Evolving changes in expression of CD45, CD45R, CD44, CD18 and very late antigen type-4 (VLA-4) also occurred following thymectomy [24].
• Systemic neutrophil intrinsic 5-lipoxygenase activity and CD18 receptor expression linked to reperfusion injury [25].
• These data suggest that administration of a CD18-blocking agent prolongs survival in a young animal model of GBS sepsis, possibly secondary to improved tissue perfusion, lung mechanics and acid-base status [26].

References