Poly(ethylene glycol)-containing hydrogels promote the release of primary granules from human blood-derived polymorphonuclear leukocytes.
Polymorphonuclear leukocytes (PMNs) are recruited to sites of injury and biomaterial implants. Once activated, PMNs can exocytose their granule subsets to recruit monocytes (MCs) and mediate MC/macrophage activation. We investigated the release of myeloperoxidase (MPO), a primary granule marker, and matrix metalloproteinase-9 (MMP-9), a tertiary granule marker, from human blood-derived PMNs cultured on poly(ethylene glycol) (PEG) hydrogels, polydimethylsiloxane (PDMS), tissue culture polystyrene (TCPS) and gelatin-PEG (GP) hydrogels, with and without the presence of the bacterial peptide formyl-Met-Leu-Phe. Supernatants from PMN cultures on PEG-containing hydrogels (i.e., PEG and GP hydrogels) had higher concentrations of MPO than those from PMN cultures on PDMS or TCPS at 2 h. PMNs on all biomaterials released comparable levels of MMP-9 at 2 h, indicating that PMNs cultured on PEG-containing hydrogels have different mechanisms of release for primary and tertiary granules. Src family kinases were involved in the release of MPO from PMNs cultured on PEG hydrogels, TCPS and GP hydrogels and in the release of MMP-9 from PMNs cultured on all four biomaterials. The increased release of primary granules from PMNs on PEG-containing hydrogels did not significantly increase MC chemotaxis, indicating that additional co-effectors in the dynamic inflammatory milieu in vivo modulate PMN-mediated MC recruitment.
Pharmaceutical Sciences Division, School of Pharmacy, University of Wisconsin-Madison, 777 Highland Avenue, Madison, Wisconsin, 53705.
Hannah Caitlin
HC
Cohen
Tyler Jacob
TJ
Lieberthal
W John
WJ
Kao
D002633:Chemotaxis; D017077:Culture Media, Conditioned / Q000737:chemistry*; D006801:Humans; D020100:Hydrogels / Q000737:chemistry*; D008262:Macrophage Activation / Q000187:drug effects; D008264:Macrophages / Q000166:cytology / Q000378:metabolism; D020780:Matrix Metalloproteinase 9 / Q000737:chemistry*; D009000:Monocytes / Q000166:cytology / Q000378:metabolism; D009240:N-Formylmethionine Leucyl-Phenylalanine / Q000494:pharmacology; D009504:Neutrophils / Q000166:cytology / Q000378:metabolism*; D011092:Polyethylene Glycols / Q000737:chemistry*; D022142:Secretory Vesicles / Q000737:chemistry*
D017077:Culture Media, Conditioned; D020100:Hydrogels; D011092:Polyethylene Glycols; D009240:N-Formylmethionine Leucyl-Phenylalanine; C579270:MMP9 protein, human; D020780:Matrix Metalloproteinase 9
Neutrophil; acute inflammation; degranulation; matrix metalloproteinase-9; myeloperoxidase; poly(ethylene glycol)