Biology subjects

Bjorkman, L. I.

Publications and source records attributed to Bjorkman, L. I..

4 recordsLinked to original sources

bioRxiv2026

Free fatty acid 2 receptor regulates the NADPH oxidase activity induced by formyl peptide receptor specific agonists

The neutrophil NADPH oxidase is activated by signals generated by formyl peptide receptor (FPR) agonists recognized by FPR1 (fMLF) and FPR2 (WKYMVM), respectively. Also, the antagonists cyclosporin H (specific for FPR1) and PBP10 (specific for FPR2) inhibit the NADPH oxidase activity when induced by the two peptide agonists. When bound to its receptor, the non-activating positive allosteric modulator Cmp58, specific for the free fatty acid 2 receptor (FFA2R), affects not only the response induced by agonists specific for FFA2R, but also the activating potency but not the efficacy of the two FPR activating peptides. Even though Cmp58 is without effect on the efficacy of the response induced by the FPR agonists, the inhibitory effect of the respective FPR specific antagonists is reduced. This sensitivity shift was reversed by an FFA2R specific antagonist suggesting that two different signals generated by the FPRs activate the NADPH oxidase. According to a receptor trans-regulation model, the activated FPRs generate signals that directly activate the NADPH oxidase and signals that activate the allosterically modulated FFA2Rs to elicit activation of the NADPH.

pharmacology and toxicology↗

bioRxiv2025

The free fatty acid 2 receptor regulates the activation potency of C5a and the sensitivity to the antagonist avacopan

The complement derived neutrophil chemoattractant C5a, is a potent activator of the neutrophil superoxide anion generating NADPH oxidase. An allosteric modulator specific for the free fatty acid 2 receptor increases the activating potency but not the efficacy of C5a. The allosteric modulator also decreases the inhibitory effect of the C5a receptor antagonist avacopan, suggesting that the NADPH oxidase is activated by two different signaling pathways downstream of the receptor for C5a. While the allosteric modulator affected the C5a-mediated activation of the NADPH oxidase, the C5a-induced rise in the intracellular concentration of free calcium ions was unaffected. The C5a receptor and the free fatty acid receptor belong to the family of G protein-coupled receptors family. Our results show that the activated C5a receptors generate signals that directly activate the NADPH oxidase and allosterically modulated free fatty acid receptors which secondarily generate signals that elicit NADPH oxidase activity. This is in line with an earlier described receptor transactivation model, by which the fatty acid receptor is activated by receptor downstream signals generated by several different neutrophil receptors to which we now add the receptor for C5a. In addition, the fatty acid receptor was higher ranked than the receptor for C5a, in the neutrophil receptor hierarchy. The dual receptor trans-regulatory effects, by which the receptor for C5a activates the fatty acid receptor and by which this receptor reduces the C5a response, represent new regulatory mechanisms of importance for the NADPH oxidase activity in neutrophils.

cell biology↗

bioRxiv2019

Core-2 O-glycans are required for Galectin-3 interaction with the osteoarthritis related protein lubricin

Synovial fluid lubricin (proteoglycan 4) is a mucin-type O-linked glycosylated (60% of the mass) biological lubricant involved in osteoarthritis (OA) development. Lubricin has been reported to be cross-linked by synovial galectin-3 on the lubricating articular surface. Here, we confirm that binding to galectin-3 depended on core-2 O-linked glycans, where surface plasmon resonance of a recombinant lubricin (rhPRG4) devoid of core-2 structures lacked binding capacity to recombinant galectin-3. Both galectin-3 levels and interactions with synovial lubricin were found to be decreased in late-stage OA patients coinciding with an increase of truncated and less sialylated core 1 O-glycans. These data suggest a defect cross-linking of surface active molecules in OA and provides novel insights into OA molecular pathology.

biochemistry↗

bioRxiv2019

Cathepsin G Degrades Synovial Fluid Lubricin: Relevance For Osteoarthritis Pathogenesis

Lubricin (PRG4) is a mucin type protein that plays an important role in maintaining normal joint function by providing lubrication and chondroprotection. Improper lubricin modification and degradation has been observed in idiopathic osteoarthritis (OA), while the detailed mechanism still remains unknown. We hypothesized that the protease cathepsin G (CG) may participate in degrading lubricin in synovial fluid (SF). The presence of endogenous CG in SF was confirmed in 16 patients with knee OA. Recombinant human lubricin (rhPRG4) and native lubricin purified from the SF of patients were incubated with exogenous CG and lubricin degradation was monitored using western blot, staining by Coomassie or Periodic Acid-Schiff in gels, and with proteomics. Full length lubricin ([~]300 kDa), was efficiently digested with CG generating a 25-kDa protein fragment, originating from the densely glycosylated mucin domain ([~]250 kDa). The 25-kDa fragment was present in the SF from OA patients, and the amount was increased after incubation with CG. A CG digest of rhPRG4 revealed 135 peptides and 72 glycopeptides, and confirmed that the protease could cleave in different domains of lubricin. Our results suggest that synovial CG may take part in the degradation of lubricin, which could affect the lubrication of OA joints.

pathology↗