Editing Macrophage (section)

=== Role in muscle regeneration ===
The first step to understanding the importance of macrophages in muscle repair, growth, and regeneration is that there are two "waves" of macrophages with the onset of damageable muscle use– subpopulations that do and do not directly have an influence on repairing muscle. The initial wave is a phagocytic population that comes along during periods of increased muscle use that are sufficient to cause muscle membrane lysis and membrane inflammation, which can enter and degrade the contents of injured muscle fibers.<ref>{{cite journal | vauthors = Krippendorf BB, Riley DA | title = Distinguishing unloading- versus reloading-induced changes in rat soleus muscle | journal = Muscle & Nerve | volume = 16 | issue = 1 | pages = 99–108 | date = January 1993 | pmid = 8423838 | doi = 10.1002/mus.880160116 | s2cid = 23012375 }}</ref><ref name="St Pierre BA, JG Tidball 1994 290–297">{{cite journal | vauthors = St Pierre BA, Tidball JG | title = Differential response of macrophage subpopulations to soleus muscle reloading after rat hindlimb suspension | journal = Journal of Applied Physiology | volume = 77 | issue = 1 | pages = 290–297 | date = July 1994 | pmid = 7961247 | doi = 10.1152/jappl.1994.77.1.290 }}</ref><ref>{{cite journal | vauthors = Tidball JG, Berchenko E, Frenette J | title = Macrophage invasion does not contribute to muscle membrane injury during inflammation | journal = Journal of Leukocyte Biology | volume = 65 | issue = 4 | pages = 492–498 | date = April 1999 | pmid = 10204578 | doi = 10.1002/jlb.65.4.492 | s2cid = 23315528 | doi-access = free }}</ref> These early-invading, phagocytic macrophages reach their highest concentration about 24 hours following the onset of some form of muscle cell injury or reloading.<ref name="Schiaffino S, Partridge T 2008 380">{{cite book|title=Skeletal Muscle Repair and Regeneration|vauthors=Schiaffino S, Partridge T|year=2008|series=Advances in Muscle Research|volume=3}}</ref> Their concentration rapidly declines after 48 hours.<ref name="St Pierre BA, JG Tidball 1994 290–297"/> The second group is the non-phagocytic types that are distributed near regenerative fibers. These peak between two and four days and remain elevated for several days while muscle tissue is rebuilding.<ref name="St Pierre BA, JG Tidball 1994 290–297"/> The first subpopulation has no direct benefit to repairing muscle, while the second non-phagocytic group does.

It is thought that macrophages release soluble substances that influence the proliferation, differentiation, growth, repair, and regeneration of muscle, but at this time the factor that is produced to mediate these effects is unknown.<ref name="Schiaffino S, Partridge T 2008 380"/> It is known that macrophages' involvement in promoting tissue repair is not muscle specific; they accumulate in numerous tissues during the healing process phase following injury.<ref name="pmid19079608">{{cite journal | vauthors = Bréchot N, Gomez E, Bignon M, Khallou-Laschet J, Dussiot M, Cazes A, Alanio-Bréchot C, Durand M, Philippe J, Silvestre JS, Van Rooijen N, Corvol P, Nicoletti A, Chazaud B, Germain S | title = Modulation of macrophage activation state protects tissue from necrosis during critical limb ischemia in thrombospondin-1-deficient mice | journal = PLOS ONE | volume = 3 | issue = 12 | pages = e3950 | year = 2008 | pmid = 19079608 | pmc = 2597179 | doi = 10.1371/journal.pone.0003950 | doi-access = free | bibcode = 2008PLoSO...3.3950B }}</ref>