{'fraction_non_alphanumeric': 0.04521432765707575, 'fraction_numerical': 0.03464474456840869, 'mean_word_length': 5.5038167938931295, 'pattern_counts': {'":': 0, '<': 0, '<?xml version=': 0, '>': 0, 'https://': 0, 'lorem ipsum': 0, 'www.': 0, 'xml': 0}, 'pii_count': 0, 'substrings_counts': 0, 'word_list_counts': {'cursed_substrings.json': 0, 'profanity_word_list.json': 0, 'sexual_word_list.json': 0, 'zh_pornsignals.json': 0}}
Characterization of two novel LPS‐binding sites in leukocyte integrin βA domain

Lipopolysaccharide (LPS), a bacterial endotoxin, triggers deleterious systemic inflammatory responses when released into blood circulation, causing organ dysfunction and death. In response to LPS stimulation, CD14 and toll‐like receptor (TLR)‐4 elicit inflammatory signaling cascades. Although leukocyte integrins (CD11b/CD18 and CD11c/CD18) were reported to bind LPS and induce nf‐Κb translocation, the evidence on such epitope location remains elusive. The present study aims to delineate the LPS‐binding sites on the integrin CD18 antigen and to design peptide(s) as potential prophylactic and/or therapeutic agents to modulate LPS effects in activated Jurkat cells. Epitope mapping analysis using a series of CD18 truncated variants revealed two putative LPS‐binding sites within the βA region (216–248 and 266–318 a.a.), which were further confirmed by point mutation studies. Inhibition assay demonstrated that the CD18‐βA266–318 peptide could block LPS binding in a dose‐dependent manner. Our data also indicated that treatment with the CD18‐peptide modulated TNF‐a mRNA transcription via the nf‐Κb signaling pathway in LPS‐activated Jurkat cells. In conclusion, we have identified two novel LPS‐binding sites located at the CD18 β A domain of leukocyte integrin, and the integrin peptide βA266–318 is shown to inhibit LPS binding and subsequent inflammatory events, having therapeutic implications to cure Gram‐negative endotoxemia.—Wong, K‐F., Luk, J. M., Cheng, R. H., Klickstein, L. B., and Fan, S‐T. Characterization of two novel LPS‐binding sites in leukocyte integrin βA domain. FASEB J. 21, 3231–3239 (2007)